Stephane Allard, MD and Peter MacGuire of Alissa Pharma explained the company’s promising approach to treating cancers like Hodgkin’s lymphoma or pancreatic cancer which over-express a certain protein on the surface of tumor cells. Alissa’s therapy targets this protein with antibodies linked to radioactive material that decays quickly. The result is destruction of tumor cells with reduced toxicity. A really compelling chat.
Highlights:
Sal Daher Introduces Stephane Allard and Peter MacGuire
What Alissa Pharma is Solving
"... Then we can look at different indication because we already have preclinical data indicating that the product, the anti-ferritin combined with the radiotherapy could work in pancreatic cancer, in hepatic cancer, and in neuroblastoma..."
How the Idea of the Product Came About
"...What you've done is you have been able to create a more usable manufacturable chemistry ... which gives you better results, more stable results of the binding of the antibodies to the radioactive tracers or radioactive therapy..."
Where Alissa Pharma is Headed
Competition
Peter MacGuire's Background
Dr. Stephane Allard's Background
ANGEL INVEST BOSTON IS SPONSORED BY:
Killing Cancer Cells with Less Toxicity
Guests: Stephane Allard and Peter MacGuire
Sal Daher: I'm really proud to say that the Angel Invest Boston podcast is sponsored by Purdue University Entrepreneurship and Peter Fasse, patent attorney at Fish & Richardson. Purdue is exceptional in its support of its faculty, faculty of its top five engineering school in helping them get their technology from the lab out to the market, out to industry, out to the clinic. Peter Fasse is also a great support to entrepreneurs. He is a patent attorney, specializing in microfluidics, and has been tremendously helpful to some of the startups which I'm involved, including a startup that came out of Purdue, Savran technologies. I'm proud to have these two sponsors for my podcast.
Sal Daher Introduces Stephane Allard and Peter MacGuire
Welcome to Angel Invest Boston, conversations of Boston's most interesting founders and angels. Today, we are privileged to be speaking with Stephane Allard, MD. Welcome, Stephane.
Stephane Allard: Thank you. Welcome.
Sal Daher: And with Peter MacGuire. Welcome, Peter.
Peter MacGuire: Many thanks, Sal. We appreciate this very much.
Sal Daher: I should thank my friend Lincoln Rathnam for connecting us, our mutual friend Lincoln Rathnam. Shout-out to Lincoln, and we'd love to have on this podcast sometime. He's not a startup guy, but he is an extremely, extremely savvy professional investor who's retired now, who has a lot to say. Anyway, very good. Stephane is the founder of Alissa Pharma. He is working on therapy for cancer, based on some work which he's been involved with for quite a while. I'll just let him explain the problem that Alissa Pharma is solving.
What Alissa Pharma is Solving
Stephane Allard: Thank you, Sal. I want to start by introducing Alissa. Alissa is a clinical stage biotech company, building on cancer immunotherapy and diagnostic platform. The Alissa has a proprietary radioimmunotherapy platform with an anti-ferritin antibody to address unmet medical need, both in oncology and hematology by targeting directly the cancer cell that overexpress ferritin on the surface of a cancer cell and are also radiosensitive. Ferritin is naturally occurring protein which regulate the proliferation, the angiogenesis, and the immune suppression, as well as iron delivery.
Sal Daher: Does the name ferritin from Latin for iron, fer en français, so it's a protein that when it's overexpressed on the surface of a tumor, it can be targeted with radiation therapy to attack the tumor.
Stephane Allard: Correct. The idea is to have an antibody which is an anti-ferritin, which is produced chemically. It's a rabbit antibody, to which we attach a radioisotope. In that case, we attach the indium for diagnostic and we attach yttrium for therapeutic. By doing that, we are able to focus the radiation strictly on the tumor cell that overexpress the ferritin.
Sal Daher: It has both a diagnostic use and a therapeutic use. Indium being a radioactive element and yttrium is another radioactive element.
Stephane Allard: We tried inject the indium-111, and then we have a map of where the tumor is located. Then, we apply the therapy with yttrium-90 and we can see the tumor shrink, where it was already viewed before with indium. Very sensitive therapy. A number of things has been done to de-risk the product. We know exactly the products, how it works. We have treated over 250 patients. We have the right dose of yttrium-90. We did dose-ranging study, and we know that for yttrium-90, we need to give 0.4 molecule of product, which is exactly the same dose used by Sibelium. There is a lot of safety information regarding the yttrium at that dose.
Sal Daher: It's the same dose used by what?
Stephane Allard: Sibelium? Sibelium is a treatment for non-Hodgkin's lymphoma. We are focusing on Hodgkin's lymphoma. Non-Hodgkin's and Hodgkin's are two very different diseases. For example, the non-Hodgkin react to the anti-CD30, anti-CD20, and those product don't work in Hodgkin's disease. Our product doesn't work in non-Hodgkin disease. It's very, very distant.
Sal Daher: The 250 patients that have received treatment on this, where are they located?
Stephane Allard: I would say 50 patients originally were treated at Johns Hopkins in Baltimore. The bulk of the patient come from the MD Anderson in Texas, in Houston. About 20 to 30 patients have been treated in France at the Curie Institute in Paris. Most of the patient have been treated come from Houston, MD Anderson. All the result of the treatment have been published in different paper by Dr. Vriesendorp. It's now available.
Sal Daher: It's very interesting.
"... Then we can look at different indication because we already have preclinical data indicating that the product, the anti-ferritin combined with the radiotherapy could work in pancreatic cancer, in hepatic cancer, and in neuroblastoma..."
Stephane Allard: What I can say at this point is with all the information that we have collected, we went to the FDA and we had a pre-IMD meeting with the FDA. The FDA allow us, considering the data that we have, to start a Phase 2 study with our product in Hodgkin lymphoma patient.
Sal Daher: That is something that's pretty far along. I have heard of projects this far along getting interest from strategic players. Have you had conversations in that direction with strategic players to see what evidence they need?
Stephane Allard: At this point, no. We only have contact some big institution both in France. We have very good connection with the Curie Institute, as well as Sloan Kettering Cancer in New York and NYU in New York. They are very interested in studying the product, but apart from those institution, we have not been in contact with either pharmaceutical company or some other big player.
Sal Daher: Now, where is the intellectual property? Where does it reside?
Stephane Allard: The anti-ferritin, polyclonal antibody, has been developed long time ago, Therefore, there is no more--
Sal Daher: That's open source?
Stephane Allard: The protection we have is an orphan drug application has been submitted in Europe as well as in the US, and has been approved in both continent. That give us 7 and 10 years respectively from the date of approval. When the product would be approved either by the FDA or EMA, then the start clock and the protection that we have is up to 8 and 10 years respectively.
The product right now is protected by an orphan drug. We also would like to submit a patent for a monoclonal antibody, a fully human monoclonal antibody with ferritin. We have already the sequence, but we need some money to develop it. Then we'll get a 20 years patent protecting the monoclonal antibody. Then we can look at different indication because we already have preclinical data indicating that the product, the anti-ferritin combined with the radiotherapy could work in pancreatic cancer, in hepatic cancer, and in neuroblastoma. Going back to pancreatic cancer, we did some preclinical study at St Bartholomew Hospital in London, and the results have been published and have been very encouraging.
Sal Daher: This is fascinating in the sense that you have a therapy that is very advanced. How is it that you got it to this point? How did you fund yourself to get to the point where you have these results to the point where you can get an IND for a Phase 2 study?
How the Idea of the Product Came About
Stephane Allard: Let's go back to the story of the product. The product was developed by Professor Vriesendorp who was the head of hematology at Johns Hopkins Hospital, and later move to MD Anderson.
Sal Daher: Let me just get some names here for the transcriber. Stephane Allard, that's S-T-E-P-H-A-N-E, Allard, A-L-L-A-R-D, MD. The researchers whose name you're mentioning now is?
Stephane Allard: Was Dr. Vriesendorf, V-R-I-E-S-E-N-D-O-R-F.
Sal Daher: Very good.
Stephane Allard: Dr. Vriesendorp was the head of hematology at Johns Hopkins Hospital.
Sal Daher: To facilitate for Americans, hematology in the US, we would say, hematology.
Stephane Allard: Then he moved to MD Anderson in the same position. He work in his lab and enroll a number of patients, which are the core of the data that we have today. Then he retire, and nobody took the technology because the technology was cumbersome in the sense that to attach a chelate, it was a multistep process, which has been streamlined. The chelate that was using was the DTPA. This has been changed to the DOTA. The difference is the binding was 60% after two hours. Now with the DOTA, the binding is 98% after 48 hours.
Sal Daher: Oh, wow.
Stephane Allard: All the data has been submitted to the FDA. We done all the tox study and all the distribution study, and there is no difference in the two products. Therefore, the FDA agreed that we move forward with the new chelate, the DOTA, which is much better, which has a much better stability data, and all the process have been streamlined and now everything can be GMP-manufactured.
"...What you've done is you have been able to create a more usable manufacturable chemistry ... which gives you better results, more stable results of the binding of the antibodies to the radioactive tracers or radioactive therapy..."
Sal Daher: To recapitulate, what you've done is you have been able to create a more usable manufacturable chemistry.
Stephane Allard: Correct.
Sal Daher: Which gives you better results, more stable results of the binding of the antibodies to the radioactive tracers or radioactive therapy. This is the breakthrough is the fact that you have been working on the chemistry side of this and have now gotten the FDA to accept that the new method of production--
Stephane Allard: New method of production, new chelate, everything has been approved, so now we have a product that can be GMP-manufactured very easily.
Sal Daher: The term you're using, new chelate, C-H-E-L-A-T-E it's a chemical process that we don't need to get into the details of that.
Stephane Allard: C-H-E-L-A-T-E is a piece of chemistry that allow the attachment of the radioisotope to the antibody.
Sal Daher: It's one of the steps in the chemistry for attaching the antibody, which is a protein, to the particles of the radioactive particles, which is so important so that the antibody binds to this overexpressed ferritin in the surface of the cancer, and then either shows the presence of the cancer cells or it attacks the the cancer cells. The patent protection that you have comes from an orphan drug designation, which from the time of approval by the FDA will give you a seven-year window of exclusive ownership of this therapy. Very interesting. It's interesting that you have this history. Where do you stand right now? What's the next step for a Alissa Pharma?
Where Alissa Pharma is Headed
Stephane Allard: The next step is to start the Phase 2 trial. That's why we're looking for raising the money to do a small Phase 2 trial to replicate the result that we already have, so therefore, the risk is marginal. The Phase 3, in order to get better results, we would like to combine our product with a PD-1 inhibitor. The PD-1 inhibitor, our product, induce inflammatory reaction at the tumor site, and that facilitate the action and the work of the PD-1 inhibitor.
Sal Daher: PD-1 inhibitor being another therapy for this type of Hodgkin's lymphoma?
Stephane Allard: Right, the top leader that I have been talking to an NYU and Sloan Kettering Cancer believe, and they told me but I don't want to quote them, that when we will combine our product with a PD-1 inhibitor, we actually could get a cure of the disease.
Sal Daher: Wow, okay.
Stephane Allard: Which is a very strong word and I don't want to use it then.
Sal Daher: No, I understand.
Peter MacGuire: When you say combining, these are two quite different drugs, is that correct?
Stephane Allard: Those are two different drug. First, you administer our product to induce the killing of the tumor cell, and at the same time there is a inflammatory reaction. A week later, you administer a PD-1 inhibitor. It has never been in our mind to combine the two product into one product. It was always be two administration, which will be done sequentially a week or 10 days apart.
Sal Daher: Is the PD-1 inhibitor under patent?
Stephane Allard: Yes. There are number of PD-1 inhibitor available right now. They are mainly the KEYTRUDA from Merck or OPDIVO from BMS. Those are the kind of product. Actually, at some point, when we will start the Phase 3, I think we need to partner with one of those big pharma, whether it's Merck, whether it's BMS, or other company whichever PD-1 inhibitor as well. I know that AstraZeneca has also one. A number of company has PD-1 inhibitor, enough detection, and we can collaborate with them.
Sal Daher: Dr. Allard, Stephane, I'm not an expert in this, I have very little knowledge in this, I'm a complete amateur, but I'm just wondering because these are drugs that are pretty big markets that if the pharmaceutical companies that have these drugs, and these drugs have been around for a while, and if there is a treatment that really increases the efficacy, it can actually lead to cures with the combination of those drugs, it would make sense that one of those players might be interested in a possible therapy that enhances their existing therapy. Because it enhances an existing business, perhaps it extends the business by seven years. I don't know when the KEYTRUDA patents Merck will expire, but it seems to me that conversations with strategic players are probably a good idea at this point.
Stephane Allard: I agree. It's a kind of discussion we did not have at this point.
Sal Daher: As I say, I have heard of strategic players taking interest in your Phase 2, but you've had very, very strong indications already, 150 patients.
Stephane Allard: 250.
Sal Daher: 250. You have quite a bit of data already. I don't know, because these things take a very long time, these collaborations. You start talking, and your grandchild might be out of kindergarten by the time something might happen, who knows, might be in primary school, that kind of timing. This is really fascinating. Do you feel free discussing what your funding needs are at present?
Peter MacGuire: Sure. I think this also talks a little bit to when we should talk to big pharma. The further along that we get, perhaps it's completing the Phase 2B, we feel that we'd be in much better position to-
Sal Daher: Oh definitely.
Peter MacGuire: -to be better off, but in the meantime, I think we'd be interested in having that conversation now nonetheless. Effectively, over the course of the next three years, and to complete the Phase 2B, that would require about $6 million. If we were to parcel that off a bit and say, "Okay, right away, what we have to do is put together the production and to improve ourselves in regard to our patent as it might relate to pancreatic, et cetera," that would take us up for about a year, and that would probably cost us perhaps $1 million to get those types of things put together.
At that point then, we'd once again be going out to raise money again, so that we'd get into the Phase 2B position to complete the Phase 2B. You could look at it in two different ways. We just want $1 million today because we'd have to go out and raise money in another year or two, or we'd like to get $6 million right now and basically get it all done immediately.
Sal Daher: We are speaking now in November of 2022 at a time when this is not the easiest time to be raising money. Lowering your targets, raising for something, a smaller amount, a nearer target. Given the current environment, maybe raising $1 million, would you be creating your own GMP facility, a good manufacturing practice facility, or would you be outsourcing this to someone else?
Stephane Allard: No, for the manufacturing, we will outsource, and we know GMP facility that can manufacture our product. Just for information, there is a product called THYMOGLOBULIN that is manufactured by Sanofi, which is exactly the same process that ours. We have been in touch with them and they have given us the people that manufacture the antibody could manufacture our antibody the same way. We would've a product which is GMP manufacturer, and in a second vendor that has already been qualified by Sanofi.
Sal Daher: Okay. Yes, once again, for listeners, GMP is good manufacturing practice. It's a standard that's required in order for using a treatment in clinical trials, in human trials.
Stephane Allard: Alissa is too small right now and will rely on GMP provider for the manufacturing of the antibody.
Sal Daher: Excellent. Okay. As I said before, this is an unusually advanced project in terms of the science and the results that you have, very, very promising results. Given the 250 patients that you've been treated and the excellent results you've had so far, chances are that in your Phase 2B study, you'll have good results. This is quite promising. Very good. Is there anything else that you'd like to cover talking about the company and where it is at this moment, before we go to the second part of our conversation, which is more about how you came to become an entrepreneur, how you became to start, how you and Peter got together, that sort of thing?
Peter MacGuire: How about competition?
Competition
Stephane Allard: Ah, the main competitor right now is ADCETRIS. It's a product from Seattle Genetic. Seattle Genetic had changed its name to Seagen.
Sal Daher: Okay. Seagen is spelled?
Stephane Allard: S-E-A-G-E-N.
Sal Daher: Seagen, okay.
Stephane Allard: The main product that they have for Hodgkin lymphoma is an antibody combined to chemotherapy. Their product is active, is the main product but it's very toxic, and the toxicity come from the chemotherapy that they use, and more than 50% have severe peripheral neuropathy and they have also a black box warning. The advantage of our therapy, at least I would choose, the combination of ferritin plus the radioisotope, is the only toxicity we have noticed is hematology toxicity with low platelet and low white cell count, and this is reversible within three or four weeks.
Sal Daher: Oh, wow.
Stephane Allard: That's why we have a very clear definition of a dose ranging study, because a lower dose has been tested, not good enough in terms of efficacy, but the higher dose was tested and the toxicity was too high. Everybody agreed that the optimal dose right now is 0.4 molecule of yttrium-90. With that, we have a very good efficacy and safety profile as well.
Sal Daher: You expect a good safety profile compared to Seagen's therapy which has a lot of side effects because of the chemotherapy aspect of it, which is not targeted. Whereas yours, yours is targeted.
Stephane Allard: That chemotherapy is targeted as well, but the product is very toxic.
Sal Daher: Okay. Very good. I want to do a very brief promo, and then we're going to get a little bit into biographies and the history of how the venture came about. We talked a little bit about that, but we didn't talk about the part with connecting with Peter. This kind of conversation that we're having here, recorded and then launched, disseminated in the form of a podcast is a learning enterprise. The Angel Invest Boston podcast is created to help people learn.
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Now in the second part of the podcast, we're going to get into a little bit of the history. Peter MacGuire, give us a brief biography of yourself.
Peter MacGuire's Background
Peter MacGuire: I have worked in the investment business since the late 1980s, starting with investment banking firms, until about the late '90s when I went to work for an investment management business, controlled by Coutts & Company the London-based bank. We stayed there for a few years. During that course of time, among other things I did is I built out a fund of funds business for hedge funds.
Sal Daher: One moment, let me just translate to people who are not in the financial. Investment banking, you were working with companies hoping to raise funding, to raise money, advising them, perhaps helping them on their raise, so you were representing companies that wanted to get funding. Then you became a fund manager which means that you are on what's so-called a buy side, in the sense that you are buying the debt or buying the equity, the stock of companies on behalf of institutional investors or mutual funds and so forth. Coutts was the investment management for institutional clients at Coutts.
Peter MacGuire: It was primarily ultra-high individuals.
Sal Daher: Okay. Basically, picking stock investments for very wealthy individuals?
Peter MacGuire: That is correct.
Sal Daher: Okay. Then the next step after that.
Peter MacGuire: At that point, I run on my own and I began working with a number of funds and I helped them raise capital for their funds.
Sal Daher: Okay. The fund of funds is a fund that invests in a bunch of funds.
Peter MacGuire: Exactly. I did that for several years pretty successfully. Along the way I ran into Lincoln Rathnam and we began talking about things that he had been working together on. We got into an agreement with a couple guys overseas about developing an emerging market private equity platform. We're somewhat successful, and
we carried that on for several years. Last of our fund, which I worked on predominantly, was somewhat successful but we never raised a second fund for that entity again.
I guess just to make this very simple, I had been working in small firms for the last 20 years. Now I've either been raising capital for funds or I've been raising capital for companies, and I usually do both at the same time, one fashion or another.
Sal Daher: Right. Ultimately, if you're raising the capital for a fund, you're raising capital to invest in companies.
Peter MacGuire: Yes.
Sal Daher: This is great. Now, Dr. Allard, could you give us precis of your background and then we'll get into how the two of you connected and created this activity that we're discussing now.
Dr. Stephane Allard's Background
Stephane Allard: Okay. I did all my study in France. I'm sure you recognize a French accent, and I worked in Paris for American company called Wyeth.
Sal Daher: Wyeth. The pharmaceutical company, Wyeth.
Stephane Allard: Then after five years, I moved to a company called Synthélabo. Synthélabo was the pharmaceutical business of L'Oréal, the cosmetic company.
Sal Daher: L'Oréal in the US, yes. Would you spell out the name of the first company?
Stephane Allard: The first company, Wyeth. W-Y-E-T-H.
Sal Daher: Okay, yes.
Stephane Allard: Then L'Oréal. L-'-O-R-E-A-L.
Sal Daher: Excellent.
Stephane Allard: I worked for Synthélabo, their pharmaceutical branch, and I was in charge of all the research unit in Europe.
Sal Daher: Would you please state the name?
Stephane Allard: Synthélabo, S-Y-N-T-H-E-L-A-B-O. In '92, I was offered the possibility to become the president of Synthélabo in the US. I moved in '93 to the US to be in charge of the US subsidiary. That was the time we were launching Ambien. I was in charge of Ambien and the order development.
Sal Daher: Ambien, the sleeping pill.
Stephane Allard: Developing some other product from the Synthélabo portfolio. In '99, the company merged with Sanofi, and I become the VP of Medical Affair of Sanofi for four years, in charge of all the product of Sanofi. I created the oncology division, my last Sanofi at the time of the merger with Aventis. Then after that, I worked in oncology. For the last 20 years, I was the Chief Medical Officer of a small biotech company called EpiCept, and then I created Alissa Pharma.
Sal Daher: Okay, so you were large, in Big Pharma for many years, then you went to work, you became a medical officer at a startup, and then you decided to create your own.
Stephane Allard: Correct.
Sal Daher: How did this come about? From this background, you're someone who has skills, you can always go to work in large pharma.
Stephane Allard: I thought it was very difficult to manage a big pharma, where there was a lot of politics involved. When in the small biotech world, we're more focusing on the result of the product. That's where I came across the anti-ferretin antibody with a partner called John Kadous that I knew from France.
Sal Daher: Ah, okay. I suspect you know too much about big pharma, and that's why you're resistant to contacting them and discussing collaborations-
Stephane Allard: No--
Sal Daher: [laughs] That's fine because you understand how ponderous, and slow-moving, complicated.
Stephane Allard: I know all the politics involved.
Sal Daher: Yes. It's funny, it is perhaps a great blessing and a curse that you know too much. Young biotech founders have very great illusions about the speed with which these large players can move and do things. I think you have a gimlet eye, a more realistic perception, but I still believe that there is a lot to be learned from interactions with big pharma, especially as your project is so advanced.
Stephane Allard: No question.
Sal Daher: Okay, you decided to become an entrepreneur because you saw the contrast between how things are done in large pharmaceutical companies, and how things are done in small, nimble biotech startups. How did this connection with Peter come about?
Stephane Allard: We were working on another project together, and then I start talking about my own project, and that's where Peter got interested and we started working together.
Sal Daher: Ah, so you ran into him in another project that you're working on? Great.
Stephane Allard: Through another project that we're working independently together.
Sal Daher: Wow. This can be very inspiring. It's not often that you have someone with your level of experience and trajectory thinking about taking the risk of starting a company. I think it's unusual in that it's the level of experience, but at the same time, I look at this, this is an unusually advanced project, which is very interesting. This is way, way beyond what I normally do because my focus is usually with an academic founder who has a technology that's not fully developed or a therapy that's not a platform that's not fully developed and has to be, raise money to develop that to get to the point. Where with a strategic player with big pharma, they might start getting involved with clinical trials. Here, [laughs] you had clinical trials already in Phase 1, which is impressive
Stephane Allard: I think the difference with Alissa Pharma is, we're not trying to raise money for an idea. We already have a product. We have already demonstrated that it works. We know the product is safe and we know that the community is looking forward to work with us to continue development and go to the next step. We have already de-risked a number of stuff.
Sal Daher: Your contention is that, it is a substantially de-risked project. I can't disagree with you, in a sense that compared to a lot of the things that I see, as I said, you're very much more mature and de-risked. Very good, very good.
[musc]
Well, Dr. Stephane Allard and Peter MacGuire of Alissa Pharma, that's spelled, A-L-I-S-S-A, Pharma, P-H-A-R-M-A, I'm very grateful to both of you for making time to be on the Angel Invest Boston podcast.
Peter MacGuire: Sal, thank you very much for doing this. This has been great. Many thanks.
Stephane Allard: Thank you.
Sal Daher: Great. This is Angel Invest Boston, thanks for listening. I'm Sal Daher.
I'm glad you were able to join us. Our engineer is Raul Rosa. Our theme was composed by John McKusick. Our graphic design is by Katharine Woodman Maynard. Our host is coached by Grace Daher.