Histogen HSC – Clinical Research Update

Hair loss research is on fire right now, and Histogen is storming forward with its trials on a new injectable hair loss treatment that showed promise with only 3 individual treatments in initial phase trials.   This is clearly superior to applying a foam to your scalp daily, or popping a pill for the rest of your life.  To monitor and track all the ongoing research projects, we have established a Pipeline Page which we encourage you to bookmark and check often.

We had the pleasure of speaking with Dr. Gail Naughton (G) and her Director of Communications, Eileen Brandt (E) this week.

Time was very limited, and we had a lot of questions to go through, so just rattling everything off in shotgun approach was the method selected.  The audio is also highly edited so it flows a bit awkwardly at times.  Below is the text from the interview presented in the video above.

Histogen HSC Interview – Dr. Gail Naughton

E:  I thought it would be best if we can start by talking about what’s related to today’s announcement.  I know that at least one of your questions pertained to our potential partner in China, and then to Histogen’s additional financing needs.

G:  Just to give you an update:  We expect before the end of August to have the final license agreement for HSC for China announced, and then shortly after that, the same for Mexico.  So maybe we can do some of the questions today, and then wait for the licenses in a couple of weeks, to do more of an in-depth – you know what the business plan is for country by country.

H:  Announcement regarding partnership with China, late stage negotiations, did those negotiations go through, is there going to be a clinical trial in China, anything like that?

G:  Huapont Life Sciences is a leading dermatology company in China, so the fact that they’ve invested in Histogen with the use of proceeds to be used to further develop HSC in the United States is a very strong statement on their behalf, and their endorsing the approach and the technology.  We have a binding term sheet with them now that is focused on an exclusive license for HSC in China, and we hope to have that full license executed by the end of August.  And at that time we’ll be able to lay out the plan for how they plan to move forward with clinical trials and commercialization in mainland China.

H:  Recently the fund raising goal was raised to a goal of $18 million.  Is Histogen almost near their goal for fund-raising and is an IPO on the horizon?

G:  Our goal is to raise an additional $11 million in the next 12 months to be able to support the upscaling of the HSC product, to be able support further research and of course getting us to the point where we can be in a state to commercialize the product in Mexico and do a Phase 3 study in the United States.  So if everything stays on track with all of the research we are doing, we expect to have additional clinical data on HSC from the US and Mexico by the end of next summer, and positive data from those trials, will, we believe, absolutely support an IPO before the end of 2017, 2018.  [Editor note:  Timelines must include the possibility of unexpected delays.  In this case, new data by Fall 2017 and IPO by Spring 2018]

H:  Follicles that grow terminal hair have DP cell counts between 1400 and 3000 cells.  Has Histogen looked into the follicles after HSC injections to see if the DP cell-count has increased?  Wouldn’t it have to, considering as far as we know, the hair size is relevant to the size of the follicle which depends on the DP cell-count.

G:  That’s a really good question.  I would love to find out what methodology people use outside of biopsy (which is not possible in a trial like this) to count the DPC cells.  We were able to use the computerized technology to evaluate not only the thickness of the hair, but the stage of the hair cycle.  So we could show that we were taking a pre-anagen follicle and making an anagen follicle.  So we did that and that of course did correlate with the thickness of the hair and the amount of terminal hairs.  I would love input, if there’s some methodology that is non-invasive, to count the DP cells, I would love to incorporate that in our upcoming clinical trials.  So more data on that would be so welcome.

H:  If the DP cell count is higher, would that mean that Histogen has figured out a way to migrate DP cells back to the DP and the follicle.  He spoke with Dr. Claire Higgins and she mentioned that a simpler method for reversing hair loss would be to get the DP cells to come back to the follicle.

G:  Again, this is only hypothetical, so we believe that we have caused them to migrate back, but we have not had a methodology to assess that.  We do know that we are causing the cells from the bulge to migrate down to the bottom of the now-elongated shaft, and migrate up the shaft to convert a vellus hair to terminal, or to create a new terminal hair.  Or more terminal hairs per shaft.  But we do not know about the DPC’s and again would love to look at that.

H:  Have you filed for Phase 2 dose-ranging study for men in America yet, and when can we expect those trials to begin recruiting, if so.

G:  So we have not filed the IND (investigational new drug application) for men yet.  We are still answering questions on the Phase 1 for women, which is the first step.  We have identified the 3 clinical centers that will be doing the Phase 2, and we are hopeful that we’ll be able to start recruiting by the end of the 1st quarter of next year.  That’s our goal.

H:  Regarding Mexico …

G:  You can say that Histogen has identified a partner in Mexico and has had several meetings with the COFEPRIS.  We are hoping to announce the full license and the clinical plan from Mexico (soon).

H:  Has Histogen also secured a partner in Japan?  As per the Histogen fact sheet from 2015, you were seeking a partnership in Japan.  It would be favorable considering the new regulation for biotech and stem cell therapies in that country.

G:  We actually had an offer from a potential partner in Japan which our board did not accept, because they feel that after solidifying China and Mexico, our goal should be to go for the rest of the world (inaudible).   And that’s what we’re focused on right now.  If the perfect partner in Japan came by, we would certainly entertain it.  But the deal that we were offered, the board said, was not supportive of what they consider licensing the crown jewel of the company.

H:  At this stage do you still anticipate it being a 3-session process?

G:  Yes, three sessions.  The Phase 3 in Mexico is designed to do 50 injections at week 0, 50 injections at week 6, and 50 injections at week 12.  That spacing is what we’ve had the best luck with in our physician IND, and what our partners and the regulatory agencies agree, should give an optimum effect for the patients treated.

H:  Of all the patients treated so far, what has been the average regrowth rate or average hair count increase from baseline?   I did see this on the slides.  So is it basically what was already presented there in the presentation?

G:  And that was for far fewer injections than what we’re moving forward with.  What you saw was after a total of 16 injections.  You have that data.  Its going to be very different after a total of 150.  So with Dr. Ziering’s study, we didn’t do a hair count.  We just did the photographs.  Of course which were very compelling.  You can even just by eyeball see that far greater than the 20% increase that we saw with the few – very small amount of doses.

H:  Have you done any brainstorming on the pricing structure?  How it might work, for example, a single fee for multiple injections, or charging per individual session.

G:  Our marketing partners are going to have the final say in all of that.  However, it’s going to be on a patient by patient basis.  If we have someone with diffuse hair loss all over their entire scalp – to be able to then take advantage of the full 3 sessions makes the most sense.  You can have other people who just have some hair loss in either the vertex, or temple recession.  In which case much fewer injections over a 2 or 3 time point would make sense.  We’re probably going to have a rolling scale for a full pre-treatment, versus a price per injection for patients who need treatment in more of a focal area.

H:  Do you anticipate that people who get this therapy are also going to need to continue with anti-DHT type treatments, antiandrogens?  Would it be beneficial, probably synergistic to also have antiandrogens involved?

G:  We’re going to be planning a post-marketing study looking at that.   Right now none of the clinical regulatory agencies want to involve treatment with another product along with HSC, because they want to release the pure results.  From a mechanism of action standpoint, with the materials in HSC – specifically Follistatin – are BMP antagonists.  And so basically the BMP as a result of the DHT, is causing a block on the stem-cell receptors and preventing them from responding to any growth factors.  The Follistatin material knocks that block off, and allows the stem cells to receive the signal to start dividing and go into a new anagen.  The experts who have reviewed our data believe that once a new anagen is created, that hair will last for as long as the hair cycle in that person would traditionally last (somewhere between 2 and 5 years – which is genetically-based as well as age-related).  So we do expect that once the hair cycle reaches completion, it will be subject once again to the DHT.  And so the patient could choose at that time to have another set of injections.  But the new anagen should last between 2 to 5 years without worrying about the DHT being present.

H:  There has been mention of the inability to “revive” follicles once they have “died”.  Why does there seem to be regrowth with HSC in this situation, but companies like Follica and Replicel state that after a certain point, this cannot be accomplished.  Theoretically if Follica can create baby hair, could HSC possibly turn those hairs terminal.

G:  That’s a very complicated question.  If something creates a vellus baby-fine hair, we have clinical data in all three trials to show that we can convert the vellus into terminal.  Right now we have focused on miniaturized hair follicles versus people who have had no hair in the area to date.  Of course you’re very familiar, and your readers are very familiar with Dr. Cotsarelis’ work (one of the founders of Follica) which says that someone who has been bald for 10 years has as many stem cells in their skin capable of becoming hair follicles, as anyone with a full head of hair.  So I think the first answer is “Yes” – if somebody can make a vellus, we should be able to convert it to a terminal, based on the data we’ve seen to date.  And if somebody can figure out (or perhaps even our material – we haven’t tried it yet) how to stimulate those stem cells to create a whole new follicle, that would certainly be transformational.

H:  Slide Subject 014 Global:  Was this one of the placebo people or something else?

E:  This was the pilot clinical trial of HSC.  In that trial each subject was their own control, and received either HSC or a placebo treatment.  So two sites HSC and two sites placebo.  If you look at the diagram in the top right, those highlighted numbers reflect HSC treatment.  So you can kind of see in this subject at 12 weeks – when they received the injections the hair must be clipped down, so its all an identical length for the photography to do an accurate hair count.  So at 12 weeks you can see that in the areas where this patient received HSC, their hair had already grown considerably compared to where it was clipped in the placebo region.  Do you see how it lines up with the diagram?  So its really just kind of anecdotal information, but interesting nonetheless.  Because we’re doing (inaudible) global photographs in this study were not how we based our analysis.  They’re based on hair counts in tiny photographed regions.

H: Do you have any data that would give you an impression on who would be *least* likely to respond?

G:  We have anywhere between an 85 and 86.5% response rate in our first two trials, and the third physician-sponsored trial, we had 100% response.  But Eileen, you could talk about the data – who responds the best perhaps?

H:  I think a lot of guys are just wondering:  “If I get this done, is it going to work for me?”

G:  The bottom line is if you have vellus hairs present, we can convert those vellus hairs to terminal hairs.  I don’t think we’ve seen any age, or ethnicity, or sex-related differences with that.

E:  Its unlike the currently-available treatments such as Rogaine and Propecia, which work best in young men who’ve just begun experiencing hair loss.  We haven’t found that difference with HSC.  I think that you’ve probably seen in some of our presentations that in older age groups, the HSC performs just as well as in young men.  In addition, unlike currently-available treatments it doesn’t only work in the vertex region of the scalp. We’ve also had excellent results in the temporal recession.

G:  Nothing’s approved to work there.   Which – that’s exciting for us.