Biotech portfolio updates – ESMO 2016, Exelixis, Abeona, Esperion and Seattle Genetics

After a two-month break here is a recap of key highlights from the September/October time frame. On the menu today: PD-1 controversies at ESMO 2016, Exelixis’ (EXEL) launch in renal cancer,  gene therapy data from Abeona (ABEO), long awaited update from Esperion (ESPR) and a positive surprise from Seattle Genetics (SGEN).

ESMO 2016 – Merck wins by a landslide (for now…)

While ESMO is typically secondary in importance to ASCO, this year’s meeting overshadowed its US counterpart (which was relatively quiet to begin with…), generating big headlines in the PD-1 arena.

The biggest news from ESMO this year was the colossal failure of BMS’s Opdivo (nivolumab) in 1st line non-small cell lung cancer (NSCLC) amplified by positive data for Merck’s Keytruda (pembrolizumab) in a similar setting. Opdivo’s negative results had already been announced with the failure being blamed on BMS’s decision to use a lower PD-L1 expression cut-off compared to what Merck used. The surprising twist at ESMO was the lack of benefit even in high (>50%) PD-L1 tumors, which leaves Opdivo out of the lucrative 1st line market.


Source: Reck M. N Engl J Med. 2016 Oct 8

This was the first time Opdivo and Keytruda (which are considered interchangeable) behaved so differently in large controlled trials. While the reasons for this discrepancy are still unclear, most people still believe the reason for Opdivo’s lack of benefit in PD-L1-high patients is more related to trial design and biomarkers rather than an inherent difference in their biological effect.

Roche added to the confusion with its OAK data in 2nd line NSCLC. As with other PD-1 agents, clinical effect improved with PD-L1 expression but in contrast to data with Keytruda and Opdivo, Rohce’s PD-L1 antibody Tecentriq (atezolizumab) improved survival across all subsets, including those with limited to no PD-L1 expression. Again, it isn’t clear whether this is a matter of patient selection or a true advantage PD-L1 mAbs (or just Tecentriq for that matter) have. Regardless, this is good news for Roche who will be well positioned to address patients who are not eligible for Keytruda 1st line due to low PD-L1 expression.

Merck’s and Roche’s wins over BMS improve their near-term market positioning but a batch of combination readouts next year may reshuffle the deck once again.

Focus shifts to combinations data in 2017

While Keytruda’s survival benefit (HR=0.60) is impressive especially given the fact that 50% of patients in the control arm crossed over to receive Keytruda, it is important to note that:

A – Keytruda is not curative and the vast majority of patients eventually progress

B – While ~25% of 1st line NSCLC patients have >50% PD-L1 levels, it is estimated that in real life only ~15% of patients will be eligible for Keytruda as the label has additional restrictions (background diseases, some cases of brain mets, specific driver mutations etc.)

In order to treat a larger portion of NSCLC patients companies are evaluating combination regimens that may potentially cover patients regardless of PDL1 status. The first wave of combination studies in NSCLC is divided to IO/IO (PD-1 + CTLA4) and IO/chemo.

IO/IO – BMS and AstraZeneca will report P3 data from their respective IO/IO combinations in 1H:17. This is BMS’s next opportunity to regain its leadership position in the NSCLC market which is predicted to be worth ~$20B globally. The company’s combination (Opdivo+Yervoy) is already approved in melanoma and each agent is clinically validated as monotherapy. This is not the case for AstraZeneca’s combo (durvalumab +  tremelimumab) which comprises two investigational agents, making the study riskier. Durvalumab targets PD-L1, which may or may not have the same effect as PD-1 antibodies like Keytruda and Opdivo. Tremelimumab, which was licensed from Pfizer, failed a P3 trial in melanoma (in contrast to BMS’s Yervoy) but it’s unclear whether the failure was related to trial design or to an inferior clinical effect.

At the meeting, BMS presented updated data from a combination trial, boasting a high response rate (43% for all patients improving up to 92% in high PD-L1 expressers) and a higher than expected rate of complete responses.


Source: BMS

IO/chemo – Merck and Roche are pursuing 1st line NSCLC by combining their PD-1/PD-L1 agents with various chemo regimens. To date, data from multiple studies demonstrated a variable response rate with some cohorts demonstrating numerically higher than expected response rates. In contrast to BMS and AZ, Merck and Roche don’t have a CTLA-4 antibody in late stage development which may have contributed to their decision to choose chemotherapy. It is important to note that all four companies are pursuing other IO/IO combinations in earlier stage studies.

At ESMO 2016, Merck presented the first randomized data which support the IO/chemo approach. Keytruda+chemo was superior to chemo alone in terms of response rate (55% vs. 29%) and PFS (13 vs. 8.9 months). OS data were still immature at the time and did not show a meaningful difference. These findings are positive and bode well for the combinability of PD-1 and chemo but they do not answer the more important question of combination vs. sequential treatment given the lack of a clear answer on OS.


Source: Merck

Roche is running four P3 trials with a variety of chemo regimens, data from which is expected to come out in 2017. Merck initiated a P3 of chemo with or without Keytruda in January 2016, which might have PFS data towards the end of 2017. In most of these studies, the primary endpoint is PFS (which should be available in 2017). As most patients in the control arm are likely to receive a PD-1 agent upon progression, generating an OS signal may prove challenging.

Still looking for the next PD1

Several years passed since the initial efficacy signals with PD-1 inhibitors which led many to hope that by this time there would be several additional effective IO agents. Unfortunately, this hasn’t materialized despite an industry-wide effort spanning tens of new agents that entered the clinic in the past 3 years. Clinical activity with new IO agents (LAG3, KIR, 4-1BB, OX40, TIM3, IDO, CD27, CD73, CSF1R etc.) has been modest at best, so these agents are now being explored in combination with PD-1/L1 antibodies.

To date, data from these combinations have been scarce and predominantly underwhelming. At ESMO, Incyte (INCY) reported results for its IDO inhibitor (epacadostat) when added to Keytruda. Although response rate and PFS in melanoma were numerically higher than what is expected with PD-1 monotherapy, the data are hard to interpret given the low sample size (n=19) and the less encouraging activity in other indications.

Many combination trials are expected to read out in 2017, including a P3 study of epacadostat + Keytruda in melanoma.

Exelixis off to a strong launch in RCC

At ESMO, Exelixis reported the long anticipated data in 1st line renal cancer (CABOSUN study), where Cabometyx beat standard of care drug, Sutent. This makes Cabometyx the only drug to show superiority over Sutent and although the trial was a P2 of 157 patients, it may be enough for approval. Two recent precedents for an approval in oncology based on P2 is Lenvima in RCC and Lilly’s Lartruvo in soft tissue sarcoma.

Last week, Exelixis reported its quarterly results which included the first full quarter since Cabometyx’s approval (April 2016). The cabo franchise (Cabometyx for RCC and Cometriq for medullary thyroid cancer) generated sales of $43M, of which $31M were for Cabometyx. According to Exelixis, in Q3 Cabometyx had a market share of 20% and 35% in new 2nd and 3rd line RCC patients, respectively.  This is encouraging especially given   Opdivo’s simultaneous launch in 2nd/3rd line RCC.

Cabometyx and Opdivo should continue to take market share from legacy products such as Afinitor and Inlyta but also expand the overall market (more patients receiving treatment, more treatment lines, longer treatment duration). The ultimate goal for both agents is 1st line approval. BMS is running a large P3 (1000+ patients) for Opdivo+Yervoy vs. Sutent that should have data in H2:17. Exelixis hopes data from CABOSUN will be enough for accelerated approval potentially towards the end 2017.

Regardless of 1st line market dynamics, it is clear Cabometyx is still far from saturating the market. Even if Opdivo+Yervoy  becomes the dominant 1st line option, Cabometyx will probably dominate the 2nd/3rd line market as it will be regarded as superior to every other approved agent. Last quarter’s run rate (~$120M annually) demonstrates that Cabometyx can easily become a $500M product in the US alone without any label expansions.  For the sake of comparison, Pfizer’s Inlyta, which demonstrated limited efficacy in 2nd line RCC (median PFS of 4.8 months and no survival benefit), had peak US sales of ~$210M.

The Cabometyx and Cotellic programs are starting to generate preliminary combination data with PD-1 agents. At ESMO, Exelixis reported encouraging signs of efficacy for Cabometyx+Opdivo in patients with various genitourinary tumors, including a response rate of 43%. The signal appears particularly strong in bladder cancer (both urothelial carcinoma and SCC of the bladder) but it is hard to distinguish between cabo’s contribution and that of Opdivo, especially without PD-L1 expression data.

For Cotellic, Genentech is pursuing combination studies with its PD-L1 agent, Tecentriq, across different indications. In 2017, there will be three pivotal trials in colon cancer and melanoma based on encouraging combination results. Most recently, Genentech reported a 50% response rate in BRAF-negative melanoma with a good duration of response. Genentech’s efforts are clearly a positive indication and provide potential upside for Exelixis, which has co-promotion rights for Cotellic in the US, but until P3 data are available in 2-3 years, the drug is unlikely to contribute significant sales to Exelixis.

Abeona reports preliminary promising data

As followers of this blog know, I am a strong believer in gene therapy and hope it will become the industry’s primary growth driver in the coming years. Based on the limited data package we have, gene therapy has clinical validation in liver diseases (hemophilia as a proof of concept) and genetic retinal diseases (RPE65 as a proof of concept).

Neurology is an emerging domain for gene therapy thanks to preliminary but provocative data from Avexis (AVXS) in SMA. Avexis’ results suggest its AAV9 gene therapy treatment leads to a remarkable clinical benefit in an otherwise fatal disease but so far there is no proof that the missing protein is actually generated in the CNS.

Last month, Abeona (ABEO) took the field one step further by demonstrating promising hints of activity in another neurologic disease, MPSIIIA (also known as Sanfilippo Syndrome A). MPSIIIA is characterized by elevated levels of certain sugars (GAGs) in the body (including the brain) caused by a mutation in an enzyme responsible for their degradation. In contrast to Avexis,   which did not present biomarker data, Abeona presented direct evidence that its gene therapy may actually reach the CNS and lead to a reduction in GAGs.


Source: Abeona Therapeutics

The data set included three patients who were given a single administration of ABO-102 and followed up for one month. Despite the limited follow up and the relatively low dose (5 X 1012 vg/kg) patients had a 25% reduction in GAG in the CSF (which mirrors levels in the brain) and a significant 57.6% reduction of GAGs in the urine. These biomarker reductions were accompanied by ~17% reduction in liver and spleen volume. These changes are comparable or better than the effect seen with other treatments in related diseases. For example, Alexion’s (ALXN) enzyme replacement therapy for MPSIIIB led to a ~10% reduction in CSF-GAG following 3 months of treatment.


Source : Alexion

Abeona’s data are very preliminary but coupled with Avexis’ clinical data imply that AAV9 can cross the blood brain barrier and produce significant amounts of protein. The main issues remain durability and corroborating the signal in additional patients. Long term safety is also a concern which will take years to answer.

Abeona’s data should be regarded as a positive read-across to REGENXBIO (RGNX), which holds key patents for AAV9 vectors and has two preclinical AAV9 programs for MPSI and MPSII (INDs expected in 1H:17).

Esperion – Another overhang removed

Esperion (ESPR) reported yet another data set that showed its drug, bempedoic acid (ETC-1002), leads to reduction in LDL-C and CRP. The study, which evaluated ETC-1002 in combination with high-dose of statins, demonstrated a placebo-adjusted LDL-C reduction of 22%, in line with prior studies, although the absolute decrease from baseline was relatively modest (13%). This means some of the effect was driven by increased LDL-C in the control group, which is not unheard of after 4 weeks of treatment and can be attributed to lifestyle changes. Safety profile was in line with prior experience but the treatment arm had more adverse events that so far appear manageable.


Source: Esperion Therapeutics

These results are important because they address concerns about drug-drug interactions with statins and ETC-1002’s ability to have an effect when the cholesterol biosynthesis pathway is significantly inhibited (evidenced by the low LDL-C baseline levels). They also demonstrate a favorable safety profile that needs to be further validated. Following discussions with the FDA, Esperion is now pursuing ETC-1002 in combination with any statin dose in its pivotal program.

Investors remain unimpressed with the data and the stock is traded below its Q3 cash position, despite having an imminent P3 program with sufficient runway to generate data in 2018. The negative sentiment stems primarily from the disappointing launch for PCSK9 antibodies, as physicians are waiting for cardiovascular outcomes trials (CVOT). Investors rightfully assume that this will also be the case with ETC-1002, especially in light of the more modest LDL-C effect. Lack of long term safety profile and lack of regulatory clarity around LDL-C reduction as an approvable endpoint also weigh on the stock.

Esperion’s near-zero enterprise value may turn it into a potential acquisition target. Despite the high risk, ETC-1002 is the only oral LDL-C and CRP reducing agent in P3 with a >$1B market potential under conservative assumptions.

Pleasant surprises from Seattle Genetics

At ESMO 2016 there were three positive data sets for novel ADCs, which is refreshing after a long period of setbacks and failures in the ADC field.

Seattle genetics (SGEN) and its partner Astellas reported impressive efficacy with two under-the-radar programs, ASG-22ME (anti- Nectin4 ADC) and ASG-15ME (anti- SLITRK6) in bladder cancer. The two ADCs demonstrated a 31%-33% response rate in the entire P1 population, which improved to 50%+ in patients who received the highest dose. These response rates compare favorably with the 15%-25% response rate typically seen with PD-(L)1 antibodies. Responses were seen in PD-(L)1 failures with a similar response rate to that observed with PD-(L)1-naïve patients, which may open the door for accelerated approval in last line patients (if efficacy is corroborated by a single-arm P2 study).

Daiichi-Sankyo presented encouraging results for its anti-HER2 ADC, DS-8201a, in HER2+ breast and gastric cancers. Response rate was ~32%, including a 42% rate in breast cancer patients who had been treated with Kadcyla (Roche’s anti-HER2 ADC powered by Immunogen’s (IMGN) technology). In contrast to most other ADCs in development, DS-8201a utilizes an uncommon mechanism for its payload (topoisomerase I inhibitor). While this payload appears less potent than tubulin or DNA binders, it appears to have a broader therapeutic window based on the high dose (8 mg/kg) that was administered without dose-limiting toxicities.

Portfolio holdings – November 6th, 2016


37 thoughts on “Biotech portfolio updates – ESMO 2016, Exelixis, Abeona, Esperion and Seattle Genetics

  1. Ohad
    As usual, well written review of the field.
    You wanted to cover KURA in one of your write-up. Could you share briefly you investment thesis – what was the main reason to add it to the portfolio?

    Since you are looking into the CNS field, do you have an opinion about NERV?


  2. Ohad,

    How will the fact that Cabometyx has outperformed Sutent effect the Opdivo+Yervoy trial? Comparing across trials is tough but if all the BMS trial does is equal the EXELvs Sutent trial, or even better it slightly, I’m not sure how many insurance companies are going to be willing to foot a combo bill.



  3. Andre (KURA) – I thought the efficacy signal they obtained in HRAS+ head and neck cancer was very encouraging with two durable ongoing responses out of 3 patients. Not a huge market but valuation is under $100M plus there may be other indications.

    Don’t know NERV well.

    Alex (TRVN) – Not sure if it’s related to CARA. In any case, TRVN will have data sooner next year so this is the crucial data point.

    BIll13 (EXEL) – That’s a good question but at the end it will all depend on data. It will hard to compare between EXEL’s P2 which was in higher risk patients and a 1000 P3 patient with a broader population. So if both are approved it will come down to pysician/patient discretion and reimbursers may or may not intervene.



  4. TRVN – the following observations from the ASA R&D day posted by IWFAL on the Biotech Values IHUB board may be the reason for the decline:

    1d) Respiratory Depression data – they quoted a statistic of only about 100 lawsuits due to Respiratory Depression adverse outcomes over a decade. And they further noted that Respiratory Depression is one of those things that produces a moderate number of close, scary calls, but generally doesn’t have longer impacts (there was a quote from one of the MDs that said they track the use of the opioid blockers and in his institution they use about about 5 per year – out of presumably 1000s of surgeries). Finally note that one of the MDs made a passing mention of respiratory depression impacting him due to middle-of-the-night calls.

    2) P&T Committee decisions – they noted that in theory the P&T Committee is supposed to make decisions that save overall cost, but in practice they have a “siloed” budget and thus it is difficult to get new drugs onto pharmacy. Two of the MDs independently noted that to get a new drug approved an MD within the institution generally has to ask and then is often approved only provisionally until they can, in fact, show the savings elsewhere.

    The issue may not be approvability but adoptability by hospitals.



  5. Hi Orad,
    Don´t know if you familiar with antibiotic companies – AKAO for instance. It´s a simple thing to know that markted antibiotikas will lose the game against fast growing resistances against it. AKAO is clinical-stage biopharmaceutical company developing novel antibacterials addressing multi-drug resistant (MDR) gram-negative infections yestday reported financial results for the third quarter of 2016, and announced the acceleration of the expected timeline for reporting results from the Phase 3 clinical trials of its lead product candidate, plazomicin, which is being developed to treat serious bacterial infections due to MDR Enterobacteriaceae, including carbapenem-resistant Enterobacteriaceae (CRE). If you interested in have an eye on this small and drastically undervalued company. Would be very interested in your opinion. Cempra (CEMP) – everybodys darling – will never make the big gains they´ve awaited – if approved by FDA but AKAO don´t seem to have a toxity problem. Risk/chance seems okay – the numbers we got telling this. A buy for you at this prices?
    Thanks, Martinelli


  6. PaulB (TRVN) – Thanks for this info. I agree that approval does not automatically lead to market acceptance, especially in hospitals. I still think that an opioid-like drug with less side effects is an attractive profile at least in some of the cases. I was under teh impression opioid utilization is higher than 5 out of 1000 in most hospitals but don’t have a specific number to give. Even in hospitals where physicians are reluctant to use opioids, a better safety profile may persuade them to do so.

    Martinelli (AKAO/CEMP) – Actually I am gradually getting into the anti-infective area on the venture side (earlier stage projects). There is wide skepticism around antibiotics among investors but I think that eventually the need will be enormous and a new wave of drugs will have to come (and incentivized). Still don’t have a strong opinion on publicly traded companies.

    Alex (INFI) – It’s an interest combination mechanistically speaking but imo it’s just another PD1 add-on like the rest of them – needs to be validated in the clinic.



  7. Hi Ohad

    Re TRVN
    I think what Paulb means regarding the 5 per 1000 number is the relatively rare need for narcan to counteract severe respiratory depression opioids cause post op. But this misses the point of why TRVN has a shot of being successful and what their expert panel presentation did a bad job of emphasizing.

    Its all about DRGs. Hospitals get paid the same for surgical care whether a patient goes home on post op day 1 or 5. Patients don’t go home after surgery if they cant ambulate or tolerate food intake most commonly, They are slow to ambulate or cant eat many times because of the side effects of opioid medications. The problem is there are many generic pain meds that are good. But i’m thinking even if TRVN shaves off even 8 hrs on average off hospitalizations, the hospitals benefit. but those studies need to be done post approval.

    Also disappointing in the company, they’re not looking at gi motility in comparison to opioids, which is a more common problem then severe respiratory depression and they are not advancing the oral form of drug until they get a partner, which I think is a missed opportunity as oral is more needed then IV

    I think good drug , but TRVN needs to get its message out better.

    Thanks for all you work on the blog. I’ve learned a lot


  8. Hey Ohad

    A lot has changed in a few days.

    EXEL back to $16… wow

    any forecasts about general biotech in the future?

    I’ve asked you before about VTGN and their ketamine-like compound for MDD. Two p2 trials will read out soon (early 2017), and those might be huge inflection points, considering the company’s very low valuation. Naures, a company with a competing/similar (but IV) ph2 candidate was acquired by AGN for $500M upfront plus milestone payments tied to development and commercial success. Mark Smith just joined as CMO from TEVA where he worked on CNS. He seems to be a top level executive. I think it bodes well for VTGN.

    Another company that looks excellent is PRTA – they keep having good readouts out of their ph1 programs – one of which, in Parkinson’s (the most risk) of the three programs, is partnered with Roche.

    Thanks for your advice, as always. I have opened positions in ABEO, AVXS, and ONCE.



  9. Hi Ohad,

    Amazing advice on your GT ideas. I am also now invested in RGNX and believe, compared to a single GT investment, it could have multiple positive catalysts even if some of its licensees fail (i.e. if CNS does not do well, there are other fields using RGNX’s AAV9).

    Regarding ESPR: In looking at their cash balance ($225MM), they expect to burn a total of $65MM. Assuming a 30% growth of cash burn due to feeding multiple trials, they probably have enough cash for 2 years. Do you think:

    1) if they were to do a follow-on, there would be significantly less buy-in this time around
    2) a partnership is more likely versus a takeout given a mid-2018 data readout?



  10. Hey Ohad
    another company that is flying somewhat under the radar is CCXI.
    they just announced positive phase 2 results in vasculities They have a broad mid-staghe pipeline and their science is unique… they are targeting pathways of inflammation, chemochine receptors, and the chemoattractant system.
    Have you ever looekd at them? what is your take?
    They are also going after NASH and I/O.


  11. roland (TRVN) – Thanks for the info, pain maangement in the hospital is an area I am still familiarizing myself with. I agree that TRVN will have to show pharmaco-economic benefit (shorter hospitalization, less compliations etc.).

    Peter (EXEL) – IMO as monotherapy Lenvima is significantly inferior (which is why it is approved only in combination with Afinitor).

    Dan – EXEL – the stock looks very strong. I guess quarterly sales and Roche’s aggressive plans with Cotellic improve investor sentiment but it is still hard for me to imagine the stock going higher.

    I am still pessimistic about the biotech sector as I expect pricing pressure to increase despite Trump’s win. The driving force is not legistlation but private insurers and PBMs.

    Don’t know VTGN and PRTA well.

    Horst (LIFE) – Still plan on adding, probably after the data if the data are reasonable. Very high risk so exposure should be low.

    Garry Xo (RGNX) – Thanks. So far GT is living up to its promise but long term risk is still high and the road will likely be bumpy. Agree re RGNX, I view it as a GT ETF.

    ESPR – Hard to predict but I don’t think they’ll do a follow on in the near future. PCSK9 CVOT data will be an important read-across next year.

    Dan (CCXI) – Haven’t looked at them for a while. I am cautious around chenokine receptors as targets but the recent AGN acquisition of TBRA has positive implications.

    Alex (GNCA ) – Not following them closely.



  12. Hi Ohad
    if you pessimistic about the biotech sector and dont think exel can move up, why not sell it now,and wait for a better entry point or just increse cash?


  13. Hey Ohad

    Just saw this note about PCSK9 by Regeneron and Sanofi–CVOT was not halted due to early success and is still ongoing….

    Note by Baird’s Brian Skorney on those results:

    “A hazard ratio of 0.802 is not a high bar, in our opinion. While we concede that trends on secondaries could be holding the study back, if the drug were truly “transformational,” the study mostly likely would have been stopped early.”

    Could it be that statins have better CVO than the PCSK9 drugs which are known to dramatically reduce cholesterol but not inflammation? (While Statins reduce both)

    The same is true for ESPR’s drug. Meaning that the CVOT readout by PCSK9 drugs’ may not acurately predict the efficacy of ESPR’s drug.

    What do you think?



  14. joe (EXEL) – Agree. The fact they sold shares (following option exercises) implies there is no imminent deal.

    Alex (EXEL) – I do plan to see at leasta portion.

    Dan (ESPR) – You can interpret this in both directions for ESPR. On the one hand, it questions te LDL-C hypothesis but on the other it implies that a statin-like drug may have an advantage (perhaps due to CRP reduction).



  15. $EXEL Insider sales were set preelection on Sept 26 when everyone thought Democrats were going to win. It does not mean that a buyout cannot be imminent. We don’t know, they might be negotiating, why is there no Japanese deal or a deal on Cabo/PD1 combinations ? If they were not planning on selling there will be a deal on this fronts already by now.


  16. Hi Ohad,

    I know you don’t comment on specific CAR-TCR companies but interested if you could share any general thoughts on the $JUNO news. The issue seems construct (not even platform) specific but the negative sentiment has hit across the sector.



  17. Alex – Sorry don’t know them well.

    Sb (ARQL) – I am still keeping a smaller position ahead of the HCC data as I believe it will fail. I am, however, optimistic about teh earlier stage programs and intend to buy more after the HCC announcement.

    curiousgeorge (EXEL) – I agree the absent of a deal for Japan is strange as the drug is already approved in the US and EU. Cabo is already being tested with Opdivo so I don’t envision a deal there for the sake of running combination studies.

    Ville (EXEL) – At $17 I tend to agree RCC potential in its current label is priced in.

    James Eslea MacDonald – Sorry but I prefer not to comment …



  18. Hey Ohad
    HTBX up on the hope that the three different presentations/posters at conferences, starting on Nov 30th will bring good results/data. Valuation, in spite of run up, is still below $60M. One of the presentations will be results in combination with opdivo (p1b).
    How come you do not like their technology? It seems very versatile, complementary to i/o, and very well tolerated, as well as (we will see soon) potentially having long-term effects (memory).

    Why are you so skeptical about their platform… is it that they have yet to show p2 results to validate technology, or merely the fact this is a vaccine play?


  19. Hi Ohad,

    BPMC just released the phase 1 results for one of their clinical programs. Biological activity of the compound was evident, but with safety signals. Do you think of the future of this FGFR4 program at BPMC?



  20. Dan (HTBX) – “Why are you so skeptical about their platform… is it that they have yet to show p2 results to validate technology, or merely the fact this is a vaccine play?”

    Both 🙂

    Liang (BPMC) – I thought data were OK and merit further testing especially in biomarker-selected patients. I agree that I had expected BPMC’s molecules to have a cleaner safety profile given the alleged optimal selectivity. The drug doesn’t look that different from other kinase inhibitors safety-wise.



  21. Hi Ohad,

    Not sure if you are still tracking CGRP, but $TEVA’s CGRP patent was upheld in late November by the European Patent Office. “…EPO issued a ruling revoking all claims in the patent relating to CGRP antagonist antibodies and maintaining but narrowing claims relating to the use of CGRP antagonist antibodies in human therapy to the prevention or treatment of headache such as migraine and cluster headache.”

    $ALDR has since dropped >25% to $23. Its 52 week high has been ~$36. Alder believes that the European ruling will have little readthrough to a US one (if the US one pops up in the future). Analysts are saying in the worst case scenario, Alder pays 10% royalty to Teva in the US, which leads to $2-$4 drop in valuation. With this, hits to valuation seem overblown — do you feel the same way? If so, do you think $ALDR at these levels is a good buy or will be a good buy? (Would you purchase some after 1H17 data) Thanks, Garry


  22. Deb (IMGN) – I agree stock is very depressed and factors in very limited pipeline upside. The CD38 (Sanofi) and mesothelin (Bayer) programs both have positive data but IMGN’s exposure is limited (making buyout unlikely) and timelines are long. The FRa and CD33 programs could generate data next year but we’ll probably have to wait until ASCO. The debt overhang isn’t helping either…

    Garry Xo (ALDR) – I agree the EU ruling isn’t a major issue but competition and clinical benefit are. ALDR still trades at 1.15B market cap which is too expensive given the uncertainty imo.

    bouschka (ARQL) – It’s a very nice twist especially following the NVS/Selexys deal but I don’t think it will have a major impact without clinical data. FGFR+ ICC and Proteus are still the dominant components in the ARQL story.



  23. I named Bridget Foy’s final 7 days and was informed they ended up NOT open up upon Xmas this yr.


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