October 5, 2023 • 48 mins
In a new episode of The Onco’Zine Brief, Peter Hofland talks with Ely Benaim, MD, the Chief Medical Officer and Executive Vice President Development at SonALAsense and Mark De Souza, Ph.D, President and Chief Executive Officer of SonALAsense.
SonALAsense was founded to create hope in the face of despair with Sonodynamic Therapy (SDT), a non-invasive therapy option using SONALA-001 in combination with Insightec’s MR-guided focused ultrasound (MRgFUS) to treat and eradicate deadly cancers like High-Grade Gliomas (HGG) that typically require debilitating brain surgery that often leads to tumor recurrence.
SonALAsense’s SDT uses SONALA-001, a proprietary formulation of aminolevulinic acid (ALA), to disrupt heme metabolism in tumor cells, increasing production of protoporphyrin, a heme precursor. From there, energy from focused ultrasound excites protoporphyrin molecules, which produce reactive oxygen species that destroy cancer cells.
Recently, Hasan Syed, MD, at Children’s National Hospital published a peer-reviewed paper on the first DIPG patient treated with SONALA-001 in the Journal of Neuro-Oncology; a major milestone for this deadly and understudied childhood disease. [1]
Hofland, Benaim and De Souza talk about new technologies in the treatment of difficult to treat cancers.
Reference
[1] Syed HR, Kilburn L, Fonseca A, Nazarian J, Oluigbo C, Myseros JS, Packer RJ, Keating RF. First-in-human sonodynamic therapy with ALA for pediatric diffuse intrinsic pontine glioma: a phase 1/2 study using low-intensity focused ultrasound : Technical communication. J Neurooncol. 2023 Apr;162(2):449-451. doi: 10.1007/s11060-023-04269-8. Epub 2023 Apr 12. PMID: 37046110.
About The Onco'Zine Brief
The Onco'Zine Brief is distributed in the United States via PRX (Public Radio Exchange). In the United Kingdom and Europe, the program is distributed via UK Health Radio (UKHR). And the program can be downloaded via most podcasts and streaming media services, including iTunes, Spotify, TuneIn, and iHeart Radio.
For more information about The Onco'Zine Brief or how to sponsor or support this public radio broadcast and podcast, visit to download our Media Kit, visit our Patreon page, or contact the sales team.
To sign up for The Onco'Zine Newsletter (open for residents of the United States only), text the word CANCER to 66866.
The Onco’Zine Brief is made possible, in part, by Java Original Coffee and Roastmasterz by Java Original Coffee.
Become a supporter of this podcast: https://www.spreaker.com/podcast/the-onco-zine-brief--2786156/support.
SonALAsense was founded to create hope in the face of despair with Sonodynamic Therapy (SDT), a non-invasive therapy option using SONALA-001 in combination with Insightec’s MR-guided focused ultrasound (MRgFUS) to treat and eradicate deadly cancers like High-Grade Gliomas (HGG) that typically require debilitating brain surgery that often leads to tumor recurrence.
SonALAsense’s SDT uses SONALA-001, a proprietary formulation of aminolevulinic acid (ALA), to disrupt heme metabolism in tumor cells, increasing production of protoporphyrin, a heme precursor. From there, energy from focused ultrasound excites protoporphyrin molecules, which produce reactive oxygen species that destroy cancer cells.
Recently, Hasan Syed, MD, at Children’s National Hospital published a peer-reviewed paper on the first DIPG patient treated with SONALA-001 in the Journal of Neuro-Oncology; a major milestone for this deadly and understudied childhood disease. [1]
Hofland, Benaim and De Souza talk about new technologies in the treatment of difficult to treat cancers.
Reference
[1] Syed HR, Kilburn L, Fonseca A, Nazarian J, Oluigbo C, Myseros JS, Packer RJ, Keating RF. First-in-human sonodynamic therapy with ALA for pediatric diffuse intrinsic pontine glioma: a phase 1/2 study using low-intensity focused ultrasound : Technical communication. J Neurooncol. 2023 Apr;162(2):449-451. doi: 10.1007/s11060-023-04269-8. Epub 2023 Apr 12. PMID: 37046110.
About The Onco'Zine Brief
The Onco'Zine Brief is distributed in the United States via PRX (Public Radio Exchange). In the United Kingdom and Europe, the program is distributed via UK Health Radio (UKHR). And the program can be downloaded via most podcasts and streaming media services, including iTunes, Spotify, TuneIn, and iHeart Radio.
For more information about The Onco'Zine Brief or how to sponsor or support this public radio broadcast and podcast, visit to download our Media Kit, visit our Patreon page, or contact the sales team.
To sign up for The Onco'Zine Newsletter (open for residents of the United States only), text the word CANCER to 66866.
The Onco’Zine Brief is made possible, in part, by Java Original Coffee and Roastmasterz by Java Original Coffee.
Become a supporter of this podcast: https://www.spreaker.com/podcast/the-onco-zine-brief--2786156/support.
Mark as Played
Transcript
Episode Transcript
Available transcripts are automatically generated. Complete accuracy is not guaranteed.
(00:12):
This is the young Gazine Brief withPeter Hofflin. In this episode of The
Ungusian Brief, I talk with doctorAli Benim and doctor Mark Desuza. Doctor
Bernim is chief medical Officer and ExecutiveVice President Development at son Alescence. He
is also a pediatric oncologist with overtwenty five years of academic and industry experience
(00:38):
developing transformative drugs and devices in oncology. Before joining the company, he was
the chief medical officer at Novokure.Doctor de Suza is President and chief executive
officer of the company. He hasover twenty years of executive and entrepreneurial experience
in the rare disease space. ANSE, the company we both are working for,
(01:00):
was founded to create hope in thephase of despair with Sono Dynamic Therapy
or SDT, a non invasive wayto treat and eradicate deadly cancers. I'm
Peter Hofland and this is the Youngestin Brief. The Youngest in Brief is
developed in collaboration with our online journalon Cosine, where you can find additional
information and the latest news about cancer, cancer diagnosis and treatment, and cancer
(01:23):
prevention. For more information on howto support this program, visit our website
at on Cosine and if you're livingin the United States and want to receive
our newsletter, text the word cancerto six six eight six six and we
will make sure that you'll receive ournewsletter, which includes an overview of the
latest news in oncology and hematology.This is the on Cosine Brief. For
(01:53):
the latest news about cancer and cancertreatment, visit our online journal on Causine
at www dot andcassine dot com.On the phone with me, you're doctor
Benim and doctor Desuza. Doctor Benimis chief medical Officer and executive vice president
Development at Sonalassense, and doctor Desuzais the company president and chief executive officer.
(02:15):
Doctor Benim and doctor Desuza, Welcometo the Kassine Brief. Now let
me start with you, doctor Desuza, before we come to talk about the
novel therapeutic approaches the company is developing. Tell me a little bit about yourself.
Oh, thank you, Peter.I'm Mark Desusa. I'm a biochemist
by training and I've been on thebusiness side of the biotech industry for over
(02:39):
twenty years. I started my careerat a company called Dieas. I spent
ten years there, and Diax wasfounded by a gentleman who was one of
the founders of Genzyme that really pioneeredthe development of first and class drugs for
rare genetic diseases. And when Iwas at Diax, I was part of
(02:59):
it team that actually developed two drugsfor a rare genetic disease called humanitary and
udema. Then I went on todo a number of other companies also in
the rare disease space. Some ofthose were in the rare skin cancer space,
and at two of those companies,I met Stuart Marcus, who was
my consulting chief medical officer in twoof these rare skin cancer companies, and
(03:25):
Stewart introduced me to the idea ofsonodynamic therapy, which is what Sonala Sense
is developing as a new modality totreat cancer. My interests in my career
really focused on three things, reallyfirst in class science, secondly, translating
that science into clinically meaningful results forpatients. And the third thing is a
(03:51):
world class set of founders and experienceddrug developers. And we've done all those
three things at Sonala Sense. We'relooking to develop our technology that's a non
invasive way to treat cancer into anew way to treat brain tumors and eventually
tumors outside the brain. And lookforward to talking more about that today.
(04:13):
Really, Bennim, tell me aboutyourself. Thank you, Peter. I'm
Elibinem and I'm the chief medical officer. I'm a pediatric he mythologist on colleges
by training specializing stem cell transplantation.Was for twelve years at Center Children's Research
Hospital, but I did a lotof clinical research and sells drugs and device
(04:39):
and later moving into industry. SoI have over twenty five years of clinical
research in drug development and drug anddevice combination development. So since I was
a little kid that wanted to takecare of kids with cancer and went to
train to one of the top placesin the world, stay there in the
(05:00):
faculty, and when I moved toindustry with the intention to move discoveries and
new therapies for patients with cancer pediatricsand adult in a much faster way that
we could have done it in theacademic world. So my career has been
in many different companies developed, likeI said, compounds, drugs, cell
(05:23):
therapy and drug device combinations to treatreally the most complicated and what I like
to call the more catastrophic type ofcancer. My previous company, it's a
company based on treating brain tumors callednovel Cure. When I was there,
the Gief medical officer and I movedinto Sonalyssans where I found a very interesting
(05:49):
cottingage technology to treat cancer in acompletely new way. So I felt that
this is the company that can makedifference in how patients are treated with very
bad, terrible solitude. Now,one thing I noticed is that the company
(06:10):
is not just saying it is tryingto change the treatment of patients diagnosed with
cancer, but you're actually eradicating cancers, including diseases like cleoblastoma or high grade
cliomas and other forms of brain cancer. Tell me a little bit more about
this, doctor Benning, this therapy. It is a completely different way of
(06:30):
treating patients, usually especially patients withbrain tumor. Even the initial presentation any
time is already devastating with many neurologicaldeficits for these patients. And the first
line of therapy is surgery, sobasically open the brain, to open the
head and go after the tumor.And most of these tumors are not round,
(06:57):
nice clean goal ball. These aretumors that really infiltrate into the brain
perancuma, and it is very hardto be able with surgery to take the
whole tumor, and unfortunately what happensis that the tumor recurs. So usually
(07:20):
what they usually therapy is to dosurgery first, then radiation, then chemotherapy.
Usually that's where you then sit andwait to see what happens. So
our therapy and I would let Marktalk more about the development of this technology,
(07:42):
but our therapy is really a neurosurgicalapproach using an IV formulation of a
drug that has been used for along time for selecting the tumors for surgery.
But our technique allows to treat thosetumors directly without having to invade this
(08:09):
skull, so no surgery, andwe use ultra sell waves to activate a
substance that eventually damage the cancer cellsand not the normal self. Basically,
this is a surgery without a scalpel. That's a fine way to describe it.
(08:31):
L As you mentioned, Peter,surgery is one option, one non
invasive option that's currently being used asradiation therapy, but it comes a bit
tremendous and debilitating side effects, andwhat we hope to do with our non
invasive sonodynamic therapy is to treat thetumor and kill the tumor selectively without affecting
(08:56):
normal tissue. Radiation has by standardas well and doesn't just kill the tumor,
but can have effects on healthy tissueas well, and that's what leads
to some of the side effects.So what we hope to do is to
use our non invasive procedure to treatbrain tumors without affecting normal tissue. And
(09:18):
the early data we have shows thatwe have encouraging and well tolerated procedure.
And you know obviously with chemotherapy thatthey're significant side effects as well. We
don't see that with our therapy.So when you look at chemotherapy, our
body's defenses to brain barrier makes itvery difficult for chemotherapy to be effective or
(09:39):
even work. It simply doesn't passthrough to where it needs to be.
Your approach is different and it's nothampered by the blood brain barrier. Can
you tell me a little bit moreabout this, doctor Discusier. So what
SODO dynamic therapy is. It's adrug device combination. The drug is actually
a nutrient that tumors need, actuallyany oxygen consuming cell needs, and it's
(10:03):
only a small molecule. It's onlya five carbon molecule, so there are
no issues whatsoever with penetration of bloodbrain barrier. Our drug readily crosses the
blood brain barrier and is taken upby tumor cells in far greater amounts than
normal cells. And tumor cells veryselectively convert to our drug into a compound
(10:28):
that is activated by the ultrasound toblow up the tumor cell. Normal cells
do not accumulate this compound, andthat's why when the ultrasound is given,
the ultrasound does not have an effecton normal cells. That's a specificity of
sonodenomic therapy. And so the smalldrug that you give a patient or that
you have is taken up by thecells, right, but then it is
(10:52):
changed in something else that has noplace in healthy cells. Is that correct?
That's exactly right, And then withfurther treatment it basically eradicates cancers.
So you can think of this nutrientI referred to being converted into a smart
bomb by the aultrasound. Let's takea short break and then We're back with
doctor Elbanim and doctor Mark Desusa.Clinical trials allow researchers to introduce new hope
(11:24):
by providing participants access to cutting edgeand potentially life saving treatments. Speak with
your doctor and visit stand Up toCancer dot org slash clinical trials to learn
more. Together, we can standup for all of us. This is
(11:46):
the young Gazine Brief with Peter Hofflandand welcome back in today's episode of the
Youngest in Brief. I'm talking withdoctor Eli Benim and doctor Marctu Susa.
I'm Peter Hoffland and this is theYoungest in Brief. One of the centers
dedicated to find a cure for braincancer in the next decade is the IV
(12:09):
Brain Tumor Center at Baroonurological Institute herein Phoenix, Arizona. The center personalizes
brain tumor therapy by the molecular underpinningsof each unique patients dictate their course of
treatment, and patients come to theIV Brain Tumor Center from around the world
to gain access to its array ofclinical trials, finding treatment options when they
(12:31):
actually have been told that there isno hope for them and that there is
no treatment option for them. Theteam of doctor NADOs and I, the
center's director of neurological oncology, establishedthe proof of concept for what you are
developing or what you have developed.Right. This proof of concept was based
on a phase zero two trial.Now tell me a little bit more about
(12:52):
this proof of concept and the zerotwo trial, because I think some of
our listeners may not necessarily know whatis zero two travel is. So this
was what the IVY did, whichis great. It was a study will
call it phase zero and then phaseone, so it was two studies in
one. Again we administer the IVYdrug you know this nutrient five a LA
(13:16):
and then the patients received the punodynamictherapy. When when to talk about face
zero. These are studies to learnabout the biology response to a tumor.
So the objective is not to curethe patient. The objective is to learn
(13:37):
the activity of a drug a therapybiologically in a patient, and a phase
one is one you want to learnhow a drug is distributed through the body
after it's given. As you know, many drugs have to be absorbed.
They go through the liver, theygo through the kidneys, so we need
(14:00):
to learn how the drug gets distributedin the body. In the case of
an IVY drug, we look,obviously it's not taken my mouth, but
it also goes through a process ofgetting discard, used and discarded by the
body. So there's something called pharmacokinetics, you know, from movement of the
(14:22):
drug through the body. So wedo what we call pik or from akinetics
to learn how the drug is outtakeby the body by the different cells and
how it is metabolizeder release. Inthis case, what was very interesting and
this is that phase zero part isdoctors and I took patients tend patients with
(14:46):
recurrent gilio blastoma, so patients thathave had already the standard of care and
have recurred and we're candidates for secondsurgeries. These patients then received a few
hours before five ALA our compound andthen they were treated with sono dynamic therapy.
(15:09):
The phase zero component was that is, the patients only received treatment on
half of the tumor. So patientsgot IVY of the five LA but since
this is a focus on ultrasound,the patients only received treatment on half of
the tumor. Well the other halfdidn't receive any treatment. And then those
(15:31):
patients four days later will have theirplan already resection corean. This is what
this is a called a phase zero. The therapy really was not given with
the idea of having a long termeffect on the patients, although as was
presented at the Society of Neuroncology meeting, some of this patient did have a
(15:54):
prolonged survival. But in our case, the objective of the study was to
look at the tumor four days afterthey treated only half of the tumor.
So four days later doctors and Iwent now to have the regular surgery exturbed
or took out the whole tumor.And remember we knew half of the tumor
(16:18):
was treated with sono dynamic therapy,the other half wasn't. And when we
look and did studies to allow usto see different what we call biomarkers of
self death. So these are biochemicalstudies that we do on the tumor to
that indicates if death is already happeninginto the tumor. We found that there
(16:42):
were two the two more common markersthat we know how to deal with cell
death were statistically significant elevated on thehalf that was treated compared to half that
was not treat So this is whatthe phase zero told us that we already
(17:03):
very early, you know, fourdays after the therapy, there was already
biochemical changes on the behalf of thetumor due to a dynamic therapy. So
in conclusion these patients, each patientserved as its own control, so half
(17:25):
that was treated and the other halfit was not treated, and we could
show that difference in between the twohalves and showed that the patients the tumors
that were the part of the tuberthat was treated already showed signs of self
death compared to the untreated side thatwas the Phase zero, and the therapy
(17:47):
was very well tolerated. At thesame time that we gave that IV drug
we tested, we took examples ofthe patients to measure the pharmacokinetics, and
we learned how to give this drugbefore the puto nycnamic therapy in how it's
eliminated by the body. So thiscombination of the data of additional biochemical efficacy,
(18:14):
the safety of the procedure, andthe pharmacokinetics of the drug that we
that were given then allows them toconclude that there was activity safety and a
product that was stable. It wasdistributed in an expected way, and that's
where we moved in now with thecurrent study, or the two current studies,
(18:37):
one in a pidiatd tumor called theIPG and again in recurring glioblastoma patients.
But now this was based on theon the activity and the drug doses
that we saw a doctor Snaia's place, right, So in this phase zero
two study, you're testing even approachworks. You may that half of the
(19:00):
brain tumor received treatment. Well theother side did not tell me a little
bit more about this. So rememberthese specials already got the standard of care
for the newly diagnosed patients. Sonow the patients completed, they had the
initial therapy, the initial surgery,the initial radiation, the initial chemotherapy.
(19:21):
Sometime later patient comes for a checkopand has again the tumor. So these
are recurring tumors. So they weretreated for the standard of care at the
beginning and they are going to gofor surgery again. So that's when we
came in. So the standard.The patients still received the standard in the
sense that they had the surgery,but before the surgery we did the sono
(19:45):
dynamic therapy half and half and whenthe tumor came out after the regular standard
of care, the surgery. Thepension plan is when we saw the different
so we did not compare to standardof therapy. What we evaluated in the
same patient was the efficacy of thetherapy in half of the tumor compared to
(20:07):
the other half of the tumor.So there was no risk for the patient
that we were giving something that wasnot proven because at the end, the
only proven therapy that the station wereplanned to get was again another surgery which
just came before the surgery. Thisis therapy took advantage that the tumor was
(20:30):
coming out to look into the biochemicalchanges after within the sono dynamic therapy.
In this zero two study, outcomeswere already seen after a very short period
of just four days after the conclusionof the initial study. Were you able
to continue treating patients correct? So, as I mentioned, you know the
(20:52):
face zero objective and phase one isreally to look into phase zero to look
at biochemical responses which we obtain,and phase one is safety and look at
the distribution of the body of thedrug through the body. So in general,
those patients are not set up tolook for really long term efficacy.
(21:15):
But as I mentioned, there isalready some presentation although the publication hasn't come
out yet, that there was somepatients that have long term responses. What
we're doing now is doing a phaseone phase two study and where we are
confirming the safety and the drug distributionthe PK in patients with GBM with recurrent
(21:41):
GBM, and then we're expanding toa phase two and that's where in a
phase two is when you look atthe efficacy and you have what they call
endpoints of efficacy like overall survival,how long did it take to the tumor
to come back if that's the case. So the objectives of the phase phase
(22:04):
one really even though we like toknow and it's great to hear if a
patient responded, that's not the objectiveface zero. Phase one. Phase two,
which is where we're conducting right now, it is where we are what
we call towering the study was thatthat means we need to have enough patients
(22:27):
to show statistically that the response iscaused by the therapy there were given and
not by chance. And this ispart of doing clinical trials and that's what
a phase two is. And eventuallyin a phase three you will compare your
(22:48):
therapy that look positive in a phasetwo and then compare it to the standard
of care, and again you haveto show statistically significant difference in between control
or standard of care group and theexperimental arm that has this new therapy,
and that's when new therapists get approvedby the FDA. So we are right
(23:11):
now in that phase two and sofar we're starting. We have to wait
to see the results of the study, but we already have a show in
the IPG in children that we startedtreating for this terrible disease that the safety
is very good. Way. Wehaven't seen any side effects of the children
(23:34):
that have been treated with this.Again, the first ten patients that were
treated in Phoenix also didn't show anyside effects. Let's take a short break
and then we're back with doctor Elebanimand doctor Mark Desusa. Sarcoma a.
(23:57):
So you've never heard that word before. For the forty people diagnosed with sarcoma
every day, it is a lifechanging word because sarcoma is cancer. Through
awareness, advocacy, and research,the Sarcoma Foundation of America is bringing hope
to the families whose lives have beenturned upside down. By a cancer they
had never heard of until diagnosis.Please do instend the fight to find the
(24:18):
cure for sarcoma. For more informationon the work of the Sarcoma Foundation of
America, go to Cure Sarcoma dotorg. This is the Young Gazine Brief
with Peter Hoffland and welcome back intoday's episode of the Ungrash. In Brief,
(24:48):
I'm talking with doctor Eli Benim anddoctor Mark Desusa. I'm Peter Hoffland,
and this is the Youngest in Brief. Now in these early studies,
you're dealing with recurring cancers, rightand for these patients it's not the first
time that they are diagnosed with clearblastoma or any other form of brain cancer.
Does that make a difference in termsof development of a particular approach?
(25:11):
So the issue is in general,let me go back to GBM. So
GBM in general and many cancers wherethey recur are very have very bad prognosis.
That means that usually the results areworse than when they're newly diagnosed.
And this is why this is becausethe patient already have received a lot of
(25:34):
therapies has created resistance. The cancersthat are very smart, they created resistant
through different mechanisms including other chromosomal mutationsor mutations of the tumor and make the
cells resistant to new therapies. Soin general happens many times than many tumors.
(25:56):
They don't have any many more thingsto offer that they recur some others.
And this is when you hear apatients say first line, that's when
they are newly diagnosed, get certaintherapy. Then when they go to their
recurr they may get a second line, and rarely there's some cancer that may
(26:17):
get a third line that are alreadyapproved. In general for second or third
line, many times patients go intoclinical trial. The way that the regulations
are written is in a way thatwe need to protect the patients and there
has to be a beneficence, haveto be a benefit of the patient of
(26:37):
getting an experimental therapy. So weneed to be sure that we don't take
away from the standard of care,that we don't give a sub optimal therapy
with a patient when there's already atherapy that already has a benefit of the
patient. So in general, incancer, treat patients in recurrence because there's
(27:02):
not that many that many therapies available, so it is ethical to approach these
patients and treated with the new therapies. To treat a first line patient,
you generally have to demonstrate in recurrendisease that there is activity to then take
the risk of bringing the therapy earlierwith the chance that you may be given
(27:30):
a sub optimal therapy compared to thestandard of care. But you know,
in our case, you know,our therapy really it's more of a neurosurgical
technique without the scaltal because we aregiving a nutrient to the body and then
coming out and doing surgery without openingthe brain, without giving side effect,
(27:56):
and then potentially you know, havinga great benefit to the patient. So
the development plan is really to tryto have enough data soon in this recurren
disease, is to bring this therapyearlier in the patients, before they get
radiation, before they get chemotherapy,even before they have to have major surgeries,
(28:19):
and try to see if we cantreat these patients, take control the
tumor, eradicate the tumor, andbefore or not give any more therapy after.
So that's basically the development plan.And one more thing about this therapy,
it is since we're giving a nutrientto the body that is only taken
(28:41):
or mostly taken by the tumor cellswhich they cannot survive without it. Then
the chances of having create resistance arevery low. While other chemotherapies or other
therapies will create resistance and what theycreate new mutations. For us, it
(29:03):
is non important. It is not. It doesn't affect our therapy if the
patient has a mutation or not,because our therapy treats patients that are rapidly
divided by the cancer cells. Soany cell that reproduces very quickly is going
to require a lot of five LAand it's going to be susceptible todynamic therapy.
(29:26):
To clarify, patients are receiving aparticular drug which is followed by a
radiologic or ultrasound approach. Is thatcorrect? Yeah, that is the case.
Since the cells cannot keep producing aproteins called him that carries ouction inside
the cell, it accumulates this whatwe call proto porphyry nine or PP nine.
(29:47):
So is the cell the maline thatcells by itself creates the cell that
the product that is susceptible to thesono dynamic therapy. While the normal cells
don't accumulate this product port frety nineon the cells. So the same machinery
what I call the glutenary glutony ofthe cells, we feed the cells for
(30:11):
them to produce their own smart cellsto commit basically gastronomic suicide. I will
call where they get Eventually, youknow, the Soto dynamic therapy will kill
the product of their own glutony.That is a very interesting approach because it
makes treatment also much safer. Rightnow, doctor Desuza, one of the
(30:34):
doctors using this approach is doctor MitchellBerger at you see as F Brain Tumor
Center in San Francisco. He madea very interesting statement suggesting that the potential
for this treatment, the treatment thatyou're developing, could turn clear blastoma from
a lethal disease to a manageable chronicdisease. If you draw a parallel with
breast cancer, I think thirty toforty years ago, mythaesthetic breast cancer was
(30:59):
very difficult to treat and in mostcases not really or hardly survivable. But
things have changed and metacetic breast cancercan be treated effectively. Is this something
that you're trying to accomplish in thetreatment of brain cancer. Yeah, that's
right, that's a great parallel thatyou drove over there from breast cancer in
Doctor Burger, who's chair of ourscientific advisory Born, you know, has
(31:22):
stated it is really our vision statement. We are still in clinical trials,
but what we are doing to tryand achieve that vision is to retreat patients.
And that's what we've just started doing, is not just treat patients once,
but to keep treating them to keeptheir tumor at bay. You know,
I'm under no illusion that we willhave a cure, but if we
(31:45):
can keep retreating patients to give patientsa decent quality of life and turn them
into survivors, that's certainly well worthdoing. In twenty nineteen, I interviewed
patients who at the time was atwenty five year survivor of metastatic breast cancer.
And today she is still a patientwith metastatic breast cancer receiving treatment,
(32:09):
but her health related quality of lifeis okay and she's able to be living
a fulfilling life. Is that somethingthat you're trying to accomplish in brain cancer?
That's right, and I think thebar is high in recurrently of glastoma,
But as Elie said, eventually,you know the right, paradigm is
to treat early and maybe I'll turnit over to him here to add anything,
(32:30):
since he has treated a lot ofpatients of these conditions. Yeah,
I think that in the case ofGBM, it is true. It is
especially patients who have recurrent disease.But one of the thinks that our therapy
has the potential of really decreased thesize of the tumor. Correct, not
(32:51):
only keep the tumor for growing,and so the hope is that reducing the
tumor, we're also in the qualityof life because I remember a lot of
these patients have some neurological symptoms thatyou know, they may have process they
may have seissures, they may haveweaknesses that may eventually get better after tumor
(33:16):
reduction. Right, you can imaginea tumor growing around a bundle of nerves
that serve a function and then havingsort of a release. So the hope
is not only make it chronic,but also improve the quality of life.
And one of the things though alot of therapies in recurrent diseases, they
(33:37):
really hamper the really make worse thequality of life. Right, So a
lot of patients that go for secondor third line therapies. You know,
their quality of life really gets affectedby the hand. If I may,
you know, we treat another typeof cancer in children, and in children,
(33:58):
you know, I am a pediatricalcollege by training, we really look
more into curing disease than making itchronic because the and if you see,
in general, pediatric cancers are curablecompared to adult and this is due to
the biology of the tumors. Pediatriccancers in general, they grow very fast
(34:20):
compared to the adults. And that'swhy prevention doesn't work very well in children
because they happen and grow very veryfast compared to for example, a colorectal
cancer that can be picked up bya colonoscopy or a processed cancer that start
checking out by PSA or a physicalexam. So in pediatrics, in which
(34:44):
we're already treating patients with the terriblebrain tumor, we have the potential not
only to make this tuber control thistumor, but my hope as a pediatric
oncology is really to have major tumordeduction with the potential on long term survival.
Patients with the IPG most of themdie between nine and a half to
(35:07):
eleven months, they only like twoto three percent survive two years. So
if we can start long term survivals, it will be great with these patients.
And I do think that any therapythat shows promise in the IPG has
(35:28):
the potential of cure. Remember wereonly now we started treating monthly with these
patience or expect more responses and potentiallythere may be combinations in the future of
different therapies that will help this pediatricpatients. So, as I said in
Marxist and GBM, the bar isvery hard, especially in recourage GBM,
(35:52):
and you know, we would loveto make this a chronic disease, but
in pediatrics I will be a littlebit more optimistic on the results that we
eventually could have. Let's take ashort break and then we're back with doctor
eleven name and doctor Mark Desusa.My name is Jane Jean. I'm the
(36:17):
chair of a computational biology department atSt. Ju Children's Research Hospital. As
a data scientist that feel so excitedabout seeing the potential impact. Not only
are the kids treated as Saint Jude, but across the world. And I
think this is a great use ofthe trust we got from our donors.
(36:37):
Finding cures saving children. Learn moreat Stjude dot org. This is the
Younger Zaine Brief with Peter Hoffland andwelcome back in today's episode of the Youngest
(37:04):
in Brief. I'm talking with doctorEli Benim and doctor Mark Desuza. I'm
Peter Hoffland and this is the Youngestin Brief. Now, you've chosen to
treat very difficult cancers like leoblastoma,but looking at your pipeline, I understand
that you're trying to adapt the technologyto many different forms of cancer, not
only brain cancer. Doctor Desuza,tell me a little bit about this approach
(37:28):
and where it may take you onthe long run. That's exactly right.
We see sonodnamic therapy as a platformtechnology. We chose to start with these
brain tumors globlastoma and diffuse intrinsic pontemlioma, the pediatric cancer, because we
know they take up our drug viathe ALA in high amounts compared to normal
(37:51):
cells in the an oral form ofALA is approved to image brain tumors image
high grate the oma's prior to surgery, so we knew that the drug there,
so we started there. We knowfrom prior work from our scientific founder
and others that a number of differentcarcinomas outside the brain take up five ALA
(38:13):
similarly in high amounts. That includesconditions such as pancreatic carcinoma and others.
So we have the potential to treata number of different cancers outside the brain,
and we're just in the stages ofexploring sonodynamic therapy and working with key
opinion leaders to prioritize these cancers outsidethe brain. So the idea is that
(38:37):
we wish to prove the concept ofsonodynamic therapy, and with doctor Sinai's pioneering
study that was the first clinical studyever done in Man with sonodynamic therapy,
we plan to continue with our ownstudies in recurrent gleo blastoma in DIPG and
eventually newly diagnosed gleoblastoma and then expandoutside the brain into tumors such as bandtreadic
(39:01):
corconoma and other cancers outside the wayto really prove that this is a platform.
So that makes it again very interestingin terms of potential of these treatment
options. Dot Benim, can youtell me a little bit about the possibility
of this platform and the treatment optionsbeyond brain cancer. I love with Mark,
you know, brought out how toview this this therapy. You have
(39:25):
to understand when when you treat inthe brain, there are certain limitations.
For years of skull. You haveto go through some type of MRI machine.
Use the ultrasound. It's a littlemore complicated. There's a terrible diseases
and you know we pick very wellbecause they do have a high outtake of
(39:45):
five ALA. But when you gooutside the the brain, you know,
imagine that now you're talking with anultrasound that you handle by hand instead of
an MRI. Right, So nowthis is where where can we use this
technology? And so you say,well, I you know ultrasound the adlemen,
(40:08):
where can I treat this? Iknow where the pancreas is. I
know how to treat it. Nowthat ultra cell technology is very advanced.
It can differenti millimeters of any organanywhere in the body. So bladder cancer
correct, and so this is eventuallyyou know, there's no toxicity. We're
(40:30):
talking here very low intensity ultrasound waves, you know, like you do for
a pregnant woman or an echo cardigraphSo you can division if you want the
sci fi vision if you want,you know, can I imagine giving ivy
five ALA and then going with yourhandheld ultra cell machine and going through different
(40:52):
parts of the body and kill itselfthat have an increased uptake of five ALA,
which will be the Madigan cells andnot the normal cells. Right,
So the potential of going almost atany organ and most types of cancer is
incredible. So obviously we have toprove this. We have to prove it
(41:13):
in the brain, and there isalready some activity it works, but it
is a platform where we have togo outside and try to treat cancers that
again has a high uptake of ALA. This therapy has been used before.
The therapy has been used for skincancers where a cream has been placed on
(41:37):
premdignant or malignant cells in the skinand then a blue light has been given.
If you go to dermatology offices,you probably have seen this blue light
on a corner. You see thereand you get the blue light. So
this therapy has been proven already outsidethe brain. And the one who who
(41:58):
did this was our founder us toa Marcus that had that company that showed
that. So we know this workoutside the brain, which just now want
to use in other places. Soour plans in the future is really to
advance the platform in multiple type ofcancer, and that obviously we need the
support of the community and the scientificcommunity to really prioritize where to go.
(42:23):
And we're going to go obviously wherethe patient the therapy is they need the
most. So obviously that's why wealso go so to the worst cancers like
the IPG and GBM. Well,this sounds not only futuristic, but very
exciting and brings home for people thatare the diagnosed with cancer, even hard
(42:44):
to treat cancers like leo blastoma.In conclusion, when you say that in
the future there will be an handhelddevice doctors can use to treat patients,
would it be potentially in a GP'soffice or is this always the realm of
an oncologist. What are you expecting? I suspect a ladder. Actually,
you know, this will still bein the realm of you know, a
(43:06):
specialist with each of the organs thatwe wind up treating. Yeah, I
agree, but we're not that faraway to having that device to be in
the oncology's office or the urlations office. So that's not that far away.
We're already in the process of lookinginto having that device and conduct clinical trials
(43:28):
in that, but eventually we hopethat to have really a foot duristic therapy
that will not have side effects,that will be easier to give, and
that could be you know, repeateduntil the treatment is effective and that we'll
have low risk for recurrence right forhaving resistance to the therapy. One more
(43:57):
thing that I would like to seeon this therapy it is that even though
we're we know how to give itand eventually there will be very extreme parameters
or how to you know, theseultracent waves get to the tumor. Each
each patient will receive a very personalizedtherapy because this this therapy will be this
(44:21):
ultrasound will be tailored every therapy tothe characteristics and the size and the response
of the tumor, which is differentthan gaining, for example, radiation therapy,
where you're still going to get radiation. Maybe you'll move, there's some
response, maybe the area where it'sgoing to be treated with the radiation will
(44:42):
be a little different, but thepatient will still will get the same amount
of radiation. Or if you getin chemotherapy and there's response of the chemotherapy,
you're not going to change the doseof the chemotherapy. You're going to
still be given the same dose.In our case, we personalize it to
the resp because there some ways thathow things get activated will have to be
(45:04):
different in between each time, howthe patient's response. So I would say
this is one of the uniqueness ofour platform. Well, with that very
positive conclusion, doctor Eli Bini anddoctor Mark de Susa, thank you so
much for joining me in the Youngestin Brief today. It was a delight
to hear about some of the reallyinteresting therapies that are right now in development
(45:30):
and where we might be able togo in the future. Thank you so
much for joining me. Thank you, Peter, Thank you Peter. In
this episode of the Youngest in Brief, I spoke with doctor Eli Benim and
doctor Mark Desusa. Doctor Benimi isChief medical Officer and Executive Vice President Development
(45:53):
at son Alescence. He is alsoa pediatric oncologist with over twenty five years
of academic an industry experience developing transformativedrugs and devices in oncology. Before joining
Sonalesscence, he was the chief medicalofficer at Novakure. Doctor Desuza is President
and Chief executive Officer of solal Escence. He has over twenty years of executive
(46:15):
and entrepreneurial experience in the rare diseasespace. Now. Sonals Sense was founded
to create hope in the phase ofdespair with Sono dynamic therapy, a non
invasive way to treat and eradicate deadlycancers like high grade liomas that typically required
debilitating brain surgery that often leads totumor recurrence. For more information about Sonallessense,
(46:37):
please visit the company's website at www. Sonalessence dot com. For more
information about the studies presented in thisprogram, please go to our online journal,
Ongozine at ongozine dot com. I'mPeter Hoffland and this is the only
say Brave for us here at theYoung Sam Brave. We want to thank
you our listeners, sponsors, andadvertisers for your ongoing support. Your support
(47:00):
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(47:24):
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sixty six, that is sixty sixeight sixty six and we will make sure
that you'll receive our newsletter which includesan overview of the latest news in oncology
(47:45):
and hematology. Thank you all andthank you for listening, and join us
again for our next episode. I'mPeter Hoffland and this is the Youngest in
Brief. The Ongazine Brief is aglobal medical educational service from the publishers of
(48:07):
Ongasine and ADC Review, the Journalof Antibody Drug Conjugates. Support for the
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(48:29):
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And does not replace your doctor's adviceand guidance. Your doctor is the
best person to answer questions about yourpersonal health. If you hear something in
this program that doesn't agree with whatyour doctor has told you, ask him
(48:51):
or her about it.
This is the young Gazine Brief withPeter Hofflin. In this episode of The
Ungusian Brief, I talk with doctorAli Benim and doctor Mark Desuza. Doctor
Bernim is chief medical Officer and ExecutiveVice President Development at son Alescence. He
is also a pediatric oncologist with overtwenty five years of academic and industry experience
(00:38):
developing transformative drugs and devices in oncology. Before joining the company, he was
the chief medical officer at Novokure.Doctor de Suza is President and chief executive
officer of the company. He hasover twenty years of executive and entrepreneurial experience
in the rare disease space. ANSE, the company we both are working for,
(01:00):
was founded to create hope in thephase of despair with Sono Dynamic Therapy
or SDT, a non invasive wayto treat and eradicate deadly cancers. I'm
Peter Hofland and this is the Youngestin Brief. The Youngest in Brief is
developed in collaboration with our online journalon Cosine, where you can find additional
information and the latest news about cancer, cancer diagnosis and treatment, and cancer
(01:23):
prevention. For more information on howto support this program, visit our website
at on Cosine and if you're livingin the United States and want to receive
our newsletter, text the word cancerto six six eight six six and we
will make sure that you'll receive ournewsletter, which includes an overview of the
latest news in oncology and hematology.This is the on Cosine Brief. For
(01:53):
the latest news about cancer and cancertreatment, visit our online journal on Causine
at www dot andcassine dot com.On the phone with me, you're doctor
Benim and doctor Desuza. Doctor Benimis chief medical Officer and executive vice president
Development at Sonalassense, and doctor Desuzais the company president and chief executive officer.
(02:15):
Doctor Benim and doctor Desuza, Welcometo the Kassine Brief. Now let
me start with you, doctor Desuza, before we come to talk about the
novel therapeutic approaches the company is developing. Tell me a little bit about yourself.
Oh, thank you, Peter.I'm Mark Desusa. I'm a biochemist
by training and I've been on thebusiness side of the biotech industry for over
(02:39):
twenty years. I started my careerat a company called Dieas. I spent
ten years there, and Diax wasfounded by a gentleman who was one of
the founders of Genzyme that really pioneeredthe development of first and class drugs for
rare genetic diseases. And when Iwas at Diax, I was part of
(02:59):
it team that actually developed two drugsfor a rare genetic disease called humanitary and
udema. Then I went on todo a number of other companies also in
the rare disease space. Some ofthose were in the rare skin cancer space,
and at two of those companies,I met Stuart Marcus, who was
my consulting chief medical officer in twoof these rare skin cancer companies, and
(03:25):
Stewart introduced me to the idea ofsonodynamic therapy, which is what Sonala Sense
is developing as a new modality totreat cancer. My interests in my career
really focused on three things, reallyfirst in class science, secondly, translating
that science into clinically meaningful results forpatients. And the third thing is a
(03:51):
world class set of founders and experienceddrug developers. And we've done all those
three things at Sonala Sense. We'relooking to develop our technology that's a non
invasive way to treat cancer into anew way to treat brain tumors and eventually
tumors outside the brain. And lookforward to talking more about that today.
(04:13):
Really, Bennim, tell me aboutyourself. Thank you, Peter. I'm
Elibinem and I'm the chief medical officer. I'm a pediatric he mythologist on colleges
by training specializing stem cell transplantation.Was for twelve years at Center Children's Research
Hospital, but I did a lotof clinical research and sells drugs and device
(04:39):
and later moving into industry. SoI have over twenty five years of clinical
research in drug development and drug anddevice combination development. So since I was
a little kid that wanted to takecare of kids with cancer and went to
train to one of the top placesin the world, stay there in the
(05:00):
faculty, and when I moved toindustry with the intention to move discoveries and
new therapies for patients with cancer pediatricsand adult in a much faster way that
we could have done it in theacademic world. So my career has been
in many different companies developed, likeI said, compounds, drugs, cell
(05:23):
therapy and drug device combinations to treatreally the most complicated and what I like
to call the more catastrophic type ofcancer. My previous company, it's a
company based on treating brain tumors callednovel Cure. When I was there,
the Gief medical officer and I movedinto Sonalyssans where I found a very interesting
(05:49):
cottingage technology to treat cancer in acompletely new way. So I felt that
this is the company that can makedifference in how patients are treated with very
bad, terrible solitude. Now,one thing I noticed is that the company
(06:10):
is not just saying it is tryingto change the treatment of patients diagnosed with
cancer, but you're actually eradicating cancers, including diseases like cleoblastoma or high grade
cliomas and other forms of brain cancer. Tell me a little bit more about
this, doctor Benning, this therapy. It is a completely different way of
(06:30):
treating patients, usually especially patients withbrain tumor. Even the initial presentation any
time is already devastating with many neurologicaldeficits for these patients. And the first
line of therapy is surgery, sobasically open the brain, to open the
head and go after the tumor.And most of these tumors are not round,
(06:57):
nice clean goal ball. These aretumors that really infiltrate into the brain
perancuma, and it is very hardto be able with surgery to take the
whole tumor, and unfortunately what happensis that the tumor recurs. So usually
(07:20):
what they usually therapy is to dosurgery first, then radiation, then chemotherapy.
Usually that's where you then sit andwait to see what happens. So
our therapy and I would let Marktalk more about the development of this technology,
(07:42):
but our therapy is really a neurosurgicalapproach using an IV formulation of a
drug that has been used for along time for selecting the tumors for surgery.
But our technique allows to treat thosetumors directly without having to invade this
(08:09):
skull, so no surgery, andwe use ultra sell waves to activate a
substance that eventually damage the cancer cellsand not the normal self. Basically,
this is a surgery without a scalpel. That's a fine way to describe it.
(08:31):
L As you mentioned, Peter,surgery is one option, one non
invasive option that's currently being used asradiation therapy, but it comes a bit
tremendous and debilitating side effects, andwhat we hope to do with our non
invasive sonodynamic therapy is to treat thetumor and kill the tumor selectively without affecting
(08:56):
normal tissue. Radiation has by standardas well and doesn't just kill the tumor,
but can have effects on healthy tissueas well, and that's what leads
to some of the side effects.So what we hope to do is to
use our non invasive procedure to treatbrain tumors without affecting normal tissue. And
(09:18):
the early data we have shows thatwe have encouraging and well tolerated procedure.
And you know obviously with chemotherapy thatthey're significant side effects as well. We
don't see that with our therapy.So when you look at chemotherapy, our
body's defenses to brain barrier makes itvery difficult for chemotherapy to be effective or
(09:39):
even work. It simply doesn't passthrough to where it needs to be.
Your approach is different and it's nothampered by the blood brain barrier. Can
you tell me a little bit moreabout this, doctor Discusier. So what
SODO dynamic therapy is. It's adrug device combination. The drug is actually
a nutrient that tumors need, actuallyany oxygen consuming cell needs, and it's
(10:03):
only a small molecule. It's onlya five carbon molecule, so there are
no issues whatsoever with penetration of bloodbrain barrier. Our drug readily crosses the
blood brain barrier and is taken upby tumor cells in far greater amounts than
normal cells. And tumor cells veryselectively convert to our drug into a compound
(10:28):
that is activated by the ultrasound toblow up the tumor cell. Normal cells
do not accumulate this compound, andthat's why when the ultrasound is given,
the ultrasound does not have an effecton normal cells. That's a specificity of
sonodenomic therapy. And so the smalldrug that you give a patient or that
you have is taken up by thecells, right, but then it is
(10:52):
changed in something else that has noplace in healthy cells. Is that correct?
That's exactly right, And then withfurther treatment it basically eradicates cancers.
So you can think of this nutrientI referred to being converted into a smart
bomb by the aultrasound. Let's takea short break and then We're back with
doctor Elbanim and doctor Mark Desusa.Clinical trials allow researchers to introduce new hope
(11:24):
by providing participants access to cutting edgeand potentially life saving treatments. Speak with
your doctor and visit stand Up toCancer dot org slash clinical trials to learn
more. Together, we can standup for all of us. This is
(11:46):
the young Gazine Brief with Peter Hofflandand welcome back in today's episode of the
Youngest in Brief. I'm talking withdoctor Eli Benim and doctor Marctu Susa.
I'm Peter Hoffland and this is theYoungest in Brief. One of the centers
dedicated to find a cure for braincancer in the next decade is the IV
(12:09):
Brain Tumor Center at Baroonurological Institute herein Phoenix, Arizona. The center personalizes
brain tumor therapy by the molecular underpinningsof each unique patients dictate their course of
treatment, and patients come to theIV Brain Tumor Center from around the world
to gain access to its array ofclinical trials, finding treatment options when they
(12:31):
actually have been told that there isno hope for them and that there is
no treatment option for them. Theteam of doctor NADOs and I, the
center's director of neurological oncology, establishedthe proof of concept for what you are
developing or what you have developed.Right. This proof of concept was based
on a phase zero two trial.Now tell me a little bit more about
(12:52):
this proof of concept and the zerotwo trial, because I think some of
our listeners may not necessarily know whatis zero two travel is. So this
was what the IVY did, whichis great. It was a study will
call it phase zero and then phaseone, so it was two studies in
one. Again we administer the IVYdrug you know this nutrient five a LA
(13:16):
and then the patients received the punodynamictherapy. When when to talk about face
zero. These are studies to learnabout the biology response to a tumor.
So the objective is not to curethe patient. The objective is to learn
(13:37):
the activity of a drug a therapybiologically in a patient, and a phase
one is one you want to learnhow a drug is distributed through the body
after it's given. As you know, many drugs have to be absorbed.
They go through the liver, theygo through the kidneys, so we need
(14:00):
to learn how the drug gets distributedin the body. In the case of
an IVY drug, we look,obviously it's not taken my mouth, but
it also goes through a process ofgetting discard, used and discarded by the
body. So there's something called pharmacokinetics, you know, from movement of the
(14:22):
drug through the body. So wedo what we call pik or from akinetics
to learn how the drug is outtakeby the body by the different cells and
how it is metabolizeder release. Inthis case, what was very interesting and
this is that phase zero part isdoctors and I took patients tend patients with
(14:46):
recurrent gilio blastoma, so patients thathave had already the standard of care and
have recurred and we're candidates for secondsurgeries. These patients then received a few
hours before five ALA our compound andthen they were treated with sono dynamic therapy.
(15:09):
The phase zero component was that is, the patients only received treatment on
half of the tumor. So patientsgot IVY of the five LA but since
this is a focus on ultrasound,the patients only received treatment on half of
the tumor. Well the other halfdidn't receive any treatment. And then those
(15:31):
patients four days later will have theirplan already resection corean. This is what
this is a called a phase zero. The therapy really was not given with
the idea of having a long termeffect on the patients, although as was
presented at the Society of Neuroncology meeting, some of this patient did have a
(15:54):
prolonged survival. But in our case, the objective of the study was to
look at the tumor four days afterthey treated only half of the tumor.
So four days later doctors and Iwent now to have the regular surgery exturbed
or took out the whole tumor.And remember we knew half of the tumor
(16:18):
was treated with sono dynamic therapy,the other half wasn't. And when we
look and did studies to allow usto see different what we call biomarkers of
self death. So these are biochemicalstudies that we do on the tumor to
that indicates if death is already happeninginto the tumor. We found that there
(16:42):
were two the two more common markersthat we know how to deal with cell
death were statistically significant elevated on thehalf that was treated compared to half that
was not treat So this is whatthe phase zero told us that we already
(17:03):
very early, you know, fourdays after the therapy, there was already
biochemical changes on the behalf of thetumor due to a dynamic therapy. So
in conclusion these patients, each patientserved as its own control, so half
(17:25):
that was treated and the other halfit was not treated, and we could
show that difference in between the twohalves and showed that the patients the tumors
that were the part of the tuberthat was treated already showed signs of self
death compared to the untreated side thatwas the Phase zero, and the therapy
(17:47):
was very well tolerated. At thesame time that we gave that IV drug
we tested, we took examples ofthe patients to measure the pharmacokinetics, and
we learned how to give this drugbefore the puto nycnamic therapy in how it's
eliminated by the body. So thiscombination of the data of additional biochemical efficacy,
(18:14):
the safety of the procedure, andthe pharmacokinetics of the drug that we
that were given then allows them toconclude that there was activity safety and a
product that was stable. It wasdistributed in an expected way, and that's
where we moved in now with thecurrent study, or the two current studies,
(18:37):
one in a pidiatd tumor called theIPG and again in recurring glioblastoma patients.
But now this was based on theon the activity and the drug doses
that we saw a doctor Snaia's place, right, So in this phase zero
two study, you're testing even approachworks. You may that half of the
(19:00):
brain tumor received treatment. Well theother side did not tell me a little
bit more about this. So rememberthese specials already got the standard of care
for the newly diagnosed patients. Sonow the patients completed, they had the
initial therapy, the initial surgery,the initial radiation, the initial chemotherapy.
(19:21):
Sometime later patient comes for a checkopand has again the tumor. So these
are recurring tumors. So they weretreated for the standard of care at the
beginning and they are going to gofor surgery again. So that's when we
came in. So the standard.The patients still received the standard in the
sense that they had the surgery,but before the surgery we did the sono
(19:45):
dynamic therapy half and half and whenthe tumor came out after the regular standard
of care, the surgery. Thepension plan is when we saw the different
so we did not compare to standardof therapy. What we evaluated in the
same patient was the efficacy of thetherapy in half of the tumor compared to
(20:07):
the other half of the tumor.So there was no risk for the patient
that we were giving something that wasnot proven because at the end, the
only proven therapy that the station wereplanned to get was again another surgery which
just came before the surgery. Thisis therapy took advantage that the tumor was
(20:30):
coming out to look into the biochemicalchanges after within the sono dynamic therapy.
In this zero two study, outcomeswere already seen after a very short period
of just four days after the conclusionof the initial study. Were you able
to continue treating patients correct? So, as I mentioned, you know the
(20:52):
face zero objective and phase one isreally to look into phase zero to look
at biochemical responses which we obtain,and phase one is safety and look at
the distribution of the body of thedrug through the body. So in general,
those patients are not set up tolook for really long term efficacy.
(21:15):
But as I mentioned, there isalready some presentation although the publication hasn't come
out yet, that there was somepatients that have long term responses. What
we're doing now is doing a phaseone phase two study and where we are
confirming the safety and the drug distributionthe PK in patients with GBM with recurrent
(21:41):
GBM, and then we're expanding toa phase two and that's where in a
phase two is when you look atthe efficacy and you have what they call
endpoints of efficacy like overall survival,how long did it take to the tumor
to come back if that's the case. So the objectives of the phase phase
(22:04):
one really even though we like toknow and it's great to hear if a
patient responded, that's not the objectiveface zero. Phase one. Phase two,
which is where we're conducting right now, it is where we are what
we call towering the study was thatthat means we need to have enough patients
(22:27):
to show statistically that the response iscaused by the therapy there were given and
not by chance. And this ispart of doing clinical trials and that's what
a phase two is. And eventuallyin a phase three you will compare your
(22:48):
therapy that look positive in a phasetwo and then compare it to the standard
of care, and again you haveto show statistically significant difference in between control
or standard of care group and theexperimental arm that has this new therapy,
and that's when new therapists get approvedby the FDA. So we are right
(23:11):
now in that phase two and sofar we're starting. We have to wait
to see the results of the study, but we already have a show in
the IPG in children that we startedtreating for this terrible disease that the safety
is very good. Way. Wehaven't seen any side effects of the children
(23:34):
that have been treated with this.Again, the first ten patients that were
treated in Phoenix also didn't show anyside effects. Let's take a short break
and then we're back with doctor Elebanimand doctor Mark Desusa. Sarcoma a.
(23:57):
So you've never heard that word before. For the forty people diagnosed with sarcoma
every day, it is a lifechanging word because sarcoma is cancer. Through
awareness, advocacy, and research,the Sarcoma Foundation of America is bringing hope
to the families whose lives have beenturned upside down. By a cancer they
had never heard of until diagnosis.Please do instend the fight to find the
(24:18):
cure for sarcoma. For more informationon the work of the Sarcoma Foundation of
America, go to Cure Sarcoma dotorg. This is the Young Gazine Brief
with Peter Hoffland and welcome back intoday's episode of the Ungrash. In Brief,
(24:48):
I'm talking with doctor Eli Benim anddoctor Mark Desusa. I'm Peter Hoffland,
and this is the Youngest in Brief. Now in these early studies,
you're dealing with recurring cancers, rightand for these patients it's not the first
time that they are diagnosed with clearblastoma or any other form of brain cancer.
Does that make a difference in termsof development of a particular approach?
(25:11):
So the issue is in general,let me go back to GBM. So
GBM in general and many cancers wherethey recur are very have very bad prognosis.
That means that usually the results areworse than when they're newly diagnosed.
And this is why this is becausethe patient already have received a lot of
(25:34):
therapies has created resistance. The cancersthat are very smart, they created resistant
through different mechanisms including other chromosomal mutationsor mutations of the tumor and make the
cells resistant to new therapies. Soin general happens many times than many tumors.
(25:56):
They don't have any many more thingsto offer that they recur some others.
And this is when you hear apatients say first line, that's when
they are newly diagnosed, get certaintherapy. Then when they go to their
recurr they may get a second line, and rarely there's some cancer that may
(26:17):
get a third line that are alreadyapproved. In general for second or third
line, many times patients go intoclinical trial. The way that the regulations
are written is in a way thatwe need to protect the patients and there
has to be a beneficence, haveto be a benefit of the patient of
(26:37):
getting an experimental therapy. So weneed to be sure that we don't take
away from the standard of care,that we don't give a sub optimal therapy
with a patient when there's already atherapy that already has a benefit of the
patient. So in general, incancer, treat patients in recurrence because there's
(27:02):
not that many that many therapies available, so it is ethical to approach these
patients and treated with the new therapies. To treat a first line patient,
you generally have to demonstrate in recurrendisease that there is activity to then take
the risk of bringing the therapy earlierwith the chance that you may be given
(27:30):
a sub optimal therapy compared to thestandard of care. But you know,
in our case, you know,our therapy really it's more of a neurosurgical
technique without the scaltal because we aregiving a nutrient to the body and then
coming out and doing surgery without openingthe brain, without giving side effect,
(27:56):
and then potentially you know, havinga great benefit to the patient. So
the development plan is really to tryto have enough data soon in this recurren
disease, is to bring this therapyearlier in the patients, before they get
radiation, before they get chemotherapy,even before they have to have major surgeries,
(28:19):
and try to see if we cantreat these patients, take control the
tumor, eradicate the tumor, andbefore or not give any more therapy after.
So that's basically the development plan.And one more thing about this therapy,
it is since we're giving a nutrientto the body that is only taken
(28:41):
or mostly taken by the tumor cellswhich they cannot survive without it. Then
the chances of having create resistance arevery low. While other chemotherapies or other
therapies will create resistance and what theycreate new mutations. For us, it
(29:03):
is non important. It is not. It doesn't affect our therapy if the
patient has a mutation or not,because our therapy treats patients that are rapidly
divided by the cancer cells. Soany cell that reproduces very quickly is going
to require a lot of five LAand it's going to be susceptible todynamic therapy.
(29:26):
To clarify, patients are receiving aparticular drug which is followed by a
radiologic or ultrasound approach. Is thatcorrect? Yeah, that is the case.
Since the cells cannot keep producing aproteins called him that carries ouction inside
the cell, it accumulates this whatwe call proto porphyry nine or PP nine.
(29:47):
So is the cell the maline thatcells by itself creates the cell that
the product that is susceptible to thesono dynamic therapy. While the normal cells
don't accumulate this product port frety nineon the cells. So the same machinery
what I call the glutenary glutony ofthe cells, we feed the cells for
(30:11):
them to produce their own smart cellsto commit basically gastronomic suicide. I will
call where they get Eventually, youknow, the Soto dynamic therapy will kill
the product of their own glutony.That is a very interesting approach because it
makes treatment also much safer. Rightnow, doctor Desuza, one of the
(30:34):
doctors using this approach is doctor MitchellBerger at you see as F Brain Tumor
Center in San Francisco. He madea very interesting statement suggesting that the potential
for this treatment, the treatment thatyou're developing, could turn clear blastoma from
a lethal disease to a manageable chronicdisease. If you draw a parallel with
breast cancer, I think thirty toforty years ago, mythaesthetic breast cancer was
(30:59):
very difficult to treat and in mostcases not really or hardly survivable. But
things have changed and metacetic breast cancercan be treated effectively. Is this something
that you're trying to accomplish in thetreatment of brain cancer. Yeah, that's
right, that's a great parallel thatyou drove over there from breast cancer in
Doctor Burger, who's chair of ourscientific advisory Born, you know, has
(31:22):
stated it is really our vision statement. We are still in clinical trials,
but what we are doing to tryand achieve that vision is to retreat patients.
And that's what we've just started doing, is not just treat patients once,
but to keep treating them to keeptheir tumor at bay. You know,
I'm under no illusion that we willhave a cure, but if we
(31:45):
can keep retreating patients to give patientsa decent quality of life and turn them
into survivors, that's certainly well worthdoing. In twenty nineteen, I interviewed
patients who at the time was atwenty five year survivor of metastatic breast cancer.
And today she is still a patientwith metastatic breast cancer receiving treatment,
(32:09):
but her health related quality of lifeis okay and she's able to be living
a fulfilling life. Is that somethingthat you're trying to accomplish in brain cancer?
That's right, and I think thebar is high in recurrently of glastoma,
But as Elie said, eventually,you know the right, paradigm is
to treat early and maybe I'll turnit over to him here to add anything,
(32:30):
since he has treated a lot ofpatients of these conditions. Yeah,
I think that in the case ofGBM, it is true. It is
especially patients who have recurrent disease.But one of the thinks that our therapy
has the potential of really decreased thesize of the tumor. Correct, not
(32:51):
only keep the tumor for growing,and so the hope is that reducing the
tumor, we're also in the qualityof life because I remember a lot of
these patients have some neurological symptoms thatyou know, they may have process they
may have seissures, they may haveweaknesses that may eventually get better after tumor
(33:16):
reduction. Right, you can imaginea tumor growing around a bundle of nerves
that serve a function and then havingsort of a release. So the hope
is not only make it chronic,but also improve the quality of life.
And one of the things though alot of therapies in recurrent diseases, they
(33:37):
really hamper the really make worse thequality of life. Right, So a
lot of patients that go for secondor third line therapies. You know,
their quality of life really gets affectedby the hand. If I may,
you know, we treat another typeof cancer in children, and in children,
(33:58):
you know, I am a pediatricalcollege by training, we really look
more into curing disease than making itchronic because the and if you see,
in general, pediatric cancers are curablecompared to adult and this is due to
the biology of the tumors. Pediatriccancers in general, they grow very fast
(34:20):
compared to the adults. And that'swhy prevention doesn't work very well in children
because they happen and grow very veryfast compared to for example, a colorectal
cancer that can be picked up bya colonoscopy or a processed cancer that start
checking out by PSA or a physicalexam. So in pediatrics, in which
(34:44):
we're already treating patients with the terriblebrain tumor, we have the potential not
only to make this tuber control thistumor, but my hope as a pediatric
oncology is really to have major tumordeduction with the potential on long term survival.
Patients with the IPG most of themdie between nine and a half to
(35:07):
eleven months, they only like twoto three percent survive two years. So
if we can start long term survivals, it will be great with these patients.
And I do think that any therapythat shows promise in the IPG has
(35:28):
the potential of cure. Remember wereonly now we started treating monthly with these
patience or expect more responses and potentiallythere may be combinations in the future of
different therapies that will help this pediatricpatients. So, as I said in
Marxist and GBM, the bar isvery hard, especially in recourage GBM,
(35:52):
and you know, we would loveto make this a chronic disease, but
in pediatrics I will be a littlebit more optimistic on the results that we
eventually could have. Let's take ashort break and then we're back with doctor
eleven name and doctor Mark Desusa.My name is Jane Jean. I'm the
(36:17):
chair of a computational biology department atSt. Ju Children's Research Hospital. As
a data scientist that feel so excitedabout seeing the potential impact. Not only
are the kids treated as Saint Jude, but across the world. And I
think this is a great use ofthe trust we got from our donors.
(36:37):
Finding cures saving children. Learn moreat Stjude dot org. This is the
Younger Zaine Brief with Peter Hoffland andwelcome back in today's episode of the Youngest
(37:04):
in Brief. I'm talking with doctorEli Benim and doctor Mark Desuza. I'm
Peter Hoffland and this is the Youngestin Brief. Now, you've chosen to
treat very difficult cancers like leoblastoma,but looking at your pipeline, I understand
that you're trying to adapt the technologyto many different forms of cancer, not
only brain cancer. Doctor Desuza,tell me a little bit about this approach
(37:28):
and where it may take you onthe long run. That's exactly right.
We see sonodnamic therapy as a platformtechnology. We chose to start with these
brain tumors globlastoma and diffuse intrinsic pontemlioma, the pediatric cancer, because we
know they take up our drug viathe ALA in high amounts compared to normal
(37:51):
cells in the an oral form ofALA is approved to image brain tumors image
high grate the oma's prior to surgery, so we knew that the drug there,
so we started there. We knowfrom prior work from our scientific founder
and others that a number of differentcarcinomas outside the brain take up five ALA
(38:13):
similarly in high amounts. That includesconditions such as pancreatic carcinoma and others.
So we have the potential to treata number of different cancers outside the brain,
and we're just in the stages ofexploring sonodynamic therapy and working with key
opinion leaders to prioritize these cancers outsidethe brain. So the idea is that
(38:37):
we wish to prove the concept ofsonodynamic therapy, and with doctor Sinai's pioneering
study that was the first clinical studyever done in Man with sonodynamic therapy,
we plan to continue with our ownstudies in recurrent gleo blastoma in DIPG and
eventually newly diagnosed gleoblastoma and then expandoutside the brain into tumors such as bandtreadic
(39:01):
corconoma and other cancers outside the wayto really prove that this is a platform.
So that makes it again very interestingin terms of potential of these treatment
options. Dot Benim, can youtell me a little bit about the possibility
of this platform and the treatment optionsbeyond brain cancer. I love with Mark,
you know, brought out how toview this this therapy. You have
(39:25):
to understand when when you treat inthe brain, there are certain limitations.
For years of skull. You haveto go through some type of MRI machine.
Use the ultrasound. It's a littlemore complicated. There's a terrible diseases
and you know we pick very wellbecause they do have a high outtake of
(39:45):
five ALA. But when you gooutside the the brain, you know,
imagine that now you're talking with anultrasound that you handle by hand instead of
an MRI. Right, So nowthis is where where can we use this
technology? And so you say,well, I you know ultrasound the adlemen,
(40:08):
where can I treat this? Iknow where the pancreas is. I
know how to treat it. Nowthat ultra cell technology is very advanced.
It can differenti millimeters of any organanywhere in the body. So bladder cancer
correct, and so this is eventuallyyou know, there's no toxicity. We're
(40:30):
talking here very low intensity ultrasound waves, you know, like you do for
a pregnant woman or an echo cardigraphSo you can division if you want the
sci fi vision if you want,you know, can I imagine giving ivy
five ALA and then going with yourhandheld ultra cell machine and going through different
(40:52):
parts of the body and kill itselfthat have an increased uptake of five ALA,
which will be the Madigan cells andnot the normal cells. Right,
So the potential of going almost atany organ and most types of cancer is
incredible. So obviously we have toprove this. We have to prove it
(41:13):
in the brain, and there isalready some activity it works, but it
is a platform where we have togo outside and try to treat cancers that
again has a high uptake of ALA. This therapy has been used before.
The therapy has been used for skincancers where a cream has been placed on
(41:37):
premdignant or malignant cells in the skinand then a blue light has been given.
If you go to dermatology offices,you probably have seen this blue light
on a corner. You see thereand you get the blue light. So
this therapy has been proven already outsidethe brain. And the one who who
(41:58):
did this was our founder us toa Marcus that had that company that showed
that. So we know this workoutside the brain, which just now want
to use in other places. Soour plans in the future is really to
advance the platform in multiple type ofcancer, and that obviously we need the
support of the community and the scientificcommunity to really prioritize where to go.
(42:23):
And we're going to go obviously wherethe patient the therapy is they need the
most. So obviously that's why wealso go so to the worst cancers like
the IPG and GBM. Well,this sounds not only futuristic, but very
exciting and brings home for people thatare the diagnosed with cancer, even hard
(42:44):
to treat cancers like leo blastoma.In conclusion, when you say that in
the future there will be an handhelddevice doctors can use to treat patients,
would it be potentially in a GP'soffice or is this always the realm of
an oncologist. What are you expecting? I suspect a ladder. Actually,
you know, this will still bein the realm of you know, a
(43:06):
specialist with each of the organs thatwe wind up treating. Yeah, I
agree, but we're not that faraway to having that device to be in
the oncology's office or the urlations office. So that's not that far away.
We're already in the process of lookinginto having that device and conduct clinical trials
(43:28):
in that, but eventually we hopethat to have really a foot duristic therapy
that will not have side effects,that will be easier to give, and
that could be you know, repeateduntil the treatment is effective and that we'll
have low risk for recurrence right forhaving resistance to the therapy. One more
(43:57):
thing that I would like to seeon this therapy it is that even though
we're we know how to give itand eventually there will be very extreme parameters
or how to you know, theseultracent waves get to the tumor. Each
each patient will receive a very personalizedtherapy because this this therapy will be this
(44:21):
ultrasound will be tailored every therapy tothe characteristics and the size and the response
of the tumor, which is differentthan gaining, for example, radiation therapy,
where you're still going to get radiation. Maybe you'll move, there's some
response, maybe the area where it'sgoing to be treated with the radiation will
(44:42):
be a little different, but thepatient will still will get the same amount
of radiation. Or if you getin chemotherapy and there's response of the chemotherapy,
you're not going to change the doseof the chemotherapy. You're going to
still be given the same dose.In our case, we personalize it to
the resp because there some ways thathow things get activated will have to be
(45:04):
different in between each time, howthe patient's response. So I would say
this is one of the uniqueness ofour platform. Well, with that very
positive conclusion, doctor Eli Bini anddoctor Mark de Susa, thank you so
much for joining me in the Youngestin Brief today. It was a delight
to hear about some of the reallyinteresting therapies that are right now in development
(45:30):
and where we might be able togo in the future. Thank you so
much for joining me. Thank you, Peter, Thank you Peter. In
this episode of the Youngest in Brief, I spoke with doctor Eli Benim and
doctor Mark Desusa. Doctor Benimi isChief medical Officer and Executive Vice President Development
(45:53):
at son Alescence. He is alsoa pediatric oncologist with over twenty five years
of academic an industry experience developing transformativedrugs and devices in oncology. Before joining
Sonalesscence, he was the chief medicalofficer at Novakure. Doctor Desuza is President
and Chief executive Officer of solal Escence. He has over twenty years of executive
(46:15):
and entrepreneurial experience in the rare diseasespace. Now. Sonals Sense was founded
to create hope in the phase ofdespair with Sono dynamic therapy, a non
invasive way to treat and eradicate deadlycancers like high grade liomas that typically required
debilitating brain surgery that often leads totumor recurrence. For more information about Sonallessense,
(46:37):
please visit the company's website at www. Sonalessence dot com. For more
information about the studies presented in thisprogram, please go to our online journal,
Ongozine at ongozine dot com. I'mPeter Hoffland and this is the only
say Brave for us here at theYoung Sam Brave. We want to thank
you our listeners, sponsors, andadvertisers for your ongoing support. Your support
(47:00):
makes it possible that you can hearthis program via PRX Public Radio Exchange and
in the United Kingdom and mainland Europevia UK Health Radio. And you can
also download our program via podcast andstreaming media including iTunes, Spotify, Audible,
Stitcher, SoundCloud and nearly anywhere youcan find the podcast. For more
information about sponsoring the Youngest in briefvisit our website at Ongusine at onguzine dot
(47:24):
com. If you're living in theUnited States and want to receive our newsletter,
text the word cancer that is cA n CR to six six eight
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that you'll receive our newsletter which includesan overview of the latest news in oncology
(47:45):
and hematology. Thank you all andthank you for listening, and join us
again for our next episode. I'mPeter Hoffland and this is the Youngest in
Brief. The Ongazine Brief is aglobal medical educational service from the publishers of
(48:07):
Ongasine and ADC Review, the Journalof Antibody Drug Conjugates. Support for the
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For more information about advertising, underwritingand sponsoring options, visit Oncasine at
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(48:29):
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in this program is not intended asa substitute for professional medical or health advice.
And does not replace your doctor's adviceand guidance. Your doctor is the
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or her about it.
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