A Busy Month for Immunogen (Part II)

For part I click here

 

At ASH 2009, Immunogen (IMGN) and its partners will present clinical data on three compounds: Sanofi-Aventis’ (SNY) SAR3419, Immunogen’s IMGN901 and Biotest’s BT-062.


SAR3419

 

SAR3419 was originally developed by Immunogen, who out-licensed it to Sanofi Aventis as part of a broad collaboration. Sanofi had previously advanced two additional drugs based on Immunogen’s technology into clinical testing, but both programs were terminated, leaving SAR3419 as the only clinical stage agent in the collaboration. Now it seems that Sanofi’s early bet on Immunogen’s technology is starting to pay off.

 

SAR3419 targets CD19 which is expressed in several blood cancers. The field of anti CD19 drugs is becoming very active and crowded, with two additional anti CD19 antibodies in clinical development: Micromet’s (MITI) blinatumomab and BMS’ (BMY) MDX-1342. All three have some level of activity in humans even though each one represents a different approach to targeting CD19 and it is still unclear which targeting strategy is better. Immunogen’s technology is currently leading the pack as it enjoys the resources of a large partner that can support an aggressive and broad development program.

 

As I discussed in a previous article, Sanofi seems quite excited about SAR3419, based on a manufacturing agreement with a Korean subcontractor and informal remarks by Sanofi and Immunogen. Adding to these was the organizers’ decision to present the SAR3419 data in an oral presentation, which probably means the data was positive enough. Based on the abstract for the presentation, which is already available, SAR3419 had clear activity in heavily pretreated Non Hodgkin Lymphoma (NHL) patients.

 

Of the 25 evaluable patients, 3 achieved a complete response and 2 achieved a partial response, resulting in an objective response rate of 20%. Furthermore, 68% of patients experienced some sort of tumor shrinkage. As a dose escalation trial, this study may under-represent SAR3419’s true activity since many of the patients did not receive the optimal dose. Therefore, it will be interesting to see actual results with more patients treated at the maximum tolerated dose. Another important factor is response duration, which is still unclear. In order to be considered clinically meaningful, SAR3419 must have a response duration of at least 6 months on average.

 

SAR3419 is carefully watched by investors in Micromet, who will also be presenting updated results from a phase I NHL study at ASH. Micromet’s blinatumomab demonstrated exceptional activity in a small number of NHL patients, with a response rate of ~92% at the highest dose tested. Micromet’s technology (BiTE) can be viewed as a competitor of Immunogen’s technology and at ASH it will be the first time the two can be evaluated for the same target, even though in different trials that cannot be directly compared.

 

SAR3419 may offer an advantage in its dosing schedule. Micromet’s blinatumomab is given as a continuous infusion for 4-8 weeks while Sanofi’s SAR3419 is given once every 3 weeks until disease progression. On the other hand, it will be very hard to match blinatumomab’s activity, even though it should be noted that the larger a trial gets, the lower the performance usually is. I addressed the advantages and disadvantages of the two technologies in a previous article on Micromet.

 

It is very hard to predict which candidate will be more successful, and assuming both agents show good efficacy, physicians and patients will choose treatment based on a combination of factors including anti-tumor activity, response duration, safety profile and patient convenience.  At the end of the day, the market is big enough for more than one anti-CD19 drug.

 

Additional presentations

 

Additional presentations to watch at ASH are phase I results for IMGN901 (wholly owned by Immunogen) and Biotest’s BT-062. The two ADCs are evaluated in two different trials for the treatment of multiple myeloma, the primary indications of the blockbusters Revlimid and Velcade. In contrast to T-DM1 and SAR3419, the data for these compounds will be less mature, with up to 30 patients in each trial. Since both studies are dose escalation trials, the results may understate the drugs’ efficacy, although it is clear both have some level of activity in this disease.

 

IMGN901

 

Data from the IMGN901 phase I trial will probably demonstrate a low level of activity and a good safety profile. Based on the abstract, IMGN901 led to a partial response in one of 23 patients, but the dose used for this patient turned out to be too toxic.  3 additional patients derived benefit from this compound in the form of minor responses. Immunogen will present data for additional patients, but based on Immunogen’s announced plans to start a phase II trial of IMGN901 in combination with Revlimid, it appears that IMGN901 is not potent enough to be developed as monotherapy.

 

IMGN901 will eventually be outlicensed in order to support late stage development. Fortunately, antibodies for multiple myeloma are in high demand and the bar for activity is rather low. A recent example is the 2008 outlicensing of Facet Biotech’s (FACT) (Formerly PDL Pharmaceuticals) elotuzumab to BMS (BMY). When the deal was signed, BMS knew that elotuzumab did not achieve objective responses as a single agent , but it did not prevent it from paying an upfront payment of $30M and committing $510M in milestones. IMGN901 is being evaluated in additional cancers, which could affect its value in a partnership deal.

 

BT-062

 

Biotest’s BT-062 is an antibody-drug conjugates (ADC) targeted against CD138, a protein well known in the context of multiple myeloma. Based on the abstract, of the 20 evaluable patients, one had a partial response with an additional patient showing a strong anti-tumor effect. Several patients showed prolonged disease stabilization as well.  Additional patients are being accrued at the maximum tolerated dose, so it will be interesting to see if more responses are achieved. 

 

Interestingly, Biotest announced its plans to launch an 80 patient phase II study for BT-062 as monotherapy. This is quite unusual for antibodies for multiple myeloma, which are usually evaluated in combination with other drugs in phase II trials. It remains to be seen whether this decision was based on additional positive data.

 

Another intriguing property is BT-062’s circulation time. According to the abstract, BT-062 gets cleared from the bloodstream at a very fast rate when given in low doses, but in patients receiving higher doses it had a better circulation time. The reason is still unclear, but this profile may imply very efficient internalization of the ADC, which might play out in Biotest’s favor, assuming that the drug exposure with the higher doses is sufficient.

 

Summary

 

In summary, Immunogen concludes 2009 as its best year ever, armed with not only a product on the verge of potential approval, but with a broad pipeline and a validated platform technology. During 2009, no new drugs entered clinical trials, but the company’s partnered pipeline matured nicely, with two compounds achieving proof of concept. On top of the clear activity, Immunogen’s technology has overcome the safety issues of earlier generation ADCs, as all of its compounds had a mild side effect profile. From a business development standpoint, the most important event was the two licenses given to Amgen. Although the timelines are not clear for these projects, having someone of Amgen’s caliber is another validation for Immunogen’s technology.

 

In 2010, Immunogen is looking at several important events. Investors can expect additional licensing deals with attractive financial terms as well as at least two new agents in clinical trials. In June, results from two additional ADCs based on Immunogen’s technology (IMGN388 and BIIB015) will be presented at the ASCO meeting.  These compounds, which entered the clinical trials in mid-2008, should have enough data for evaluating their merit. Finally, the second half of 2010 could see the approval of T-DM1 for advanced breast cancer, triggering a substantial milestone payment to Immunogen.

 

Together with its competitors, Seattle Genetics (SGEN) and Micromet, Immunogen is leading the paradigm shift in the biotech industry towards next generation antibodies. For more on this trend and its implications, click here.

 

                               The Biotech Portfolio as of Dec 1st, 2009

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43 thoughts on “A Busy Month for Immunogen (Part II)

  1. Ohad,

    I have no private question for you. I just wan’t to thank you for your great analysis.

    Regards
    Toby

  2. miti question: haven’t heard much about their bite-converted commercial products. what happened to their bite-herceptin, bite-xolair, bite-erbitux?

  3. These antibodies are still patent protected so MITI cannot use them without permission. What I believe MITI is doing, is developing BiTE antibodies for the same targets but with their own proprietary antibodies.
    BiTE against EGFR ( target of Erbitux/Vectibix)has very good data.
    I didn’t see a BiTE against Her2 probably because the target is blocked.
    Xolair doesn’t target an antigen on cells, so it wouldn’t be a good choice.
    Another promising target is CD33 (Mylotarg’s target), because to date all efforts to develop a safe and effective antibody didn’t go too well.

    But the beauty with this technology that it opens up so many opportunities with new targets. Theoretically, BiTE has the widest application of all antibody platforms, even wider than antibody drug conjugates.

    ohad

  4. Hello Ohad,

    a question to another antibody company of your portfolio.

    Seattle Genetics released new data for SGN-35 on Dec. 7, 2009 from a Phase I trial in lyphoma.

    They reported: “Grade 3 neuropathies emerged in approximately 10 percent of patients after treatment at higher weekly doses, generally beyond six months of therapy.”

    Do you see trouble with this adverse events? I think SGN-35 is acutal the main asset of Seattle Genetics.

    Regards
    Toby

  5. Hi Toby,

    SGN-35 is SGEN’s main asset indeed and its safety profile looks pretty good. The safety issues you describe do not look like a show stopper, especially given the challenging patient population.

    ohad

  6. Hello Ohad,

    have you an opinion about the new press release (Dec. 13) from CLDX about CDX-011?

    The results with patients and whose tumors expressed GPNMB are very encouraging.

    Regards
    Toby

  7. Hi Toby,

    I agree, this is one of the most promising antibodies in development, although I would like to see a sample size larger than 7…
    There are signs of preferential activity in a predefined patient population, which is exactly what everyone is looking for.

    ohad

  8. Incyte is approaching $10 and I remember you said would face resistance at about $9 because of the convertible bonds and that incyte is not “cheap”. At what price point would you consider Incyte fairly valued?

  9. Thanks guys.

    Unfortunately, I am swamped with work so I will probably have time to write again only next month or so.

    Don’t know ADXS.

    Ohad

  10. I wonder why IMGN has dropped 20% year to date on little or no negative news?

    How is the data on mdvn?

  11. Ohad,

    big update out of MITI on the 10th, Do you have any thought on this recent investors day????

    Thanks

    heymang

  12. Ohad, The biotechs have sold off nicely, esp. oncology. Time to buy? IMGN now at $6.50. EXCEL, ARQL, ARRY are also at more reasonable levels. Is it up from here to ASCO? What do you think of MELA. The company seems to have a very affordable device to effectively detect melanoma skin cancer — approval decision nears. Thanks. JR

  13. pyramidhunt- Probably a result of lack of clarity regarding T-DM1’s near term fate. Turns out that despite the great results in 3rd line patients, approval is not a sure thing. I don’t know whether that’s because Roche wants to be on hte safe side or whether the FDA has become more stringent.

    heymang – The design of the pivotal trial in ALL is a big positive surprise. Other than that, things are still looking good. I’d say that the only issue was the DLTs observed at the 90ug/m2 dose in the NHL study. It remains to be seen how high MT110 reaches, because it will probably need to reach a higher dose to have clinical activity in established solid tumors.

    JR – I agree on all 4. Personally, bought more IMGN and ARQL. Plan to buy more EXEL .

    Sam – See above.

    Best,
    Ohad

  14. Hello Ohad,

    Your articles are very interesting and enjoy reading them. Do you have any idea when you will write another article? What biotech company do you plan on writing about next?
    Thanks

  15. Thanks, Sam.
    I’ll try to publish something in a couple of weeks time. Still haven’t decided what companies to write about, plenty to choose from…

    Ohad

  16. ITMN just narrowly recieved a positive recommendation (FDA might request a new phase 3 trial).

    EXEL is down more than 7% today after laying off 250 works/restructing.

    Can you give a few names that you are considering to publish?

    Thanks,
    Sam

  17. You have spoken much about cldx except that you were kinda neutral on it after crgn was bought out.

    CLDX 011 formerly onwed by crgn…you were positive about its promising effects on breast cancer while not assigning much value to the skin cnacer conidtion, however, its olds news but they reported positive news in december (old news).

    However, CDX -110 results will be released out mid year and it showed promising results before when it extended survival from 26 months vs 15 months from temodar.

    Seems like there might be surprise to the upside?

    Do you still consider cldx just a hold?

  18. ARQL more than doubled in price today when it reported a phase II trial showed that its ARQ 197 drug candidate demonstrated a 66% improvement in median Progression-Free Survival (PFS) in patients with advanced, refractory non-small cell lung cancer (NSCLC) when used in combination with erlotinib.

    ARQL was a sleepy stock until today.

  19. Well done ARQL! They rightfully earned this one with their well designed clinical program and solid execution.

    Too bad the article I was going to publish this weekend is no longer relevant…

    ohad

  20. Hi Ohad,

    it would still be very interesting to read the article on ARQL. I would appreciate if you would publish it.

    Also: Congratulations!

    With best regards,

    Sepp

  21. Sepp,

    It’s no longer relevant as it discusses the phase II study prior to the data published today.
    Send me an email and I’ll send you a copy.

    ohad

  22. Ohad,

    What do you think about the secondary offering from MITI? Do you think the stock is starting to get expensive? Do you believe MITI will go at it alone with MT103 or are you looking at them partnering it again(outside the US at least)?

  23. I also would enjoy reading the aricle you were going to publish and appreciate it if you can email it to me, too?

    My email is pyramidhunt@yahoo.com

    Arqle is now only up about 65% down from about 115%.

    Volume was over 400 times the daily average today.

    Do you believe you positive results is fully affected in the stock’s price?

  24. hi ohad,

    looks like miti is using cetuximab as their basis for bite-egfr

    Poster Title: “Evidence of a therapeutic window with a T cell-engaging BiTE antibody based on monoclonal antibody cetuximab (Erbitux)”

    Presentation Date/Time: Monday, April 19, 2010, 2 – 5 PM ET

    Presenter: Ralf Lutterbuese, Micromet

    Abstract Number: 2429

  25. sam, it’s hard to say until data is published two months from now at ASCO (I suppose). Anyway, there’s much more to ARQL than this specific trial, although no doubt it’s a very big thing.

    Ohad

  26. biotech_fan,

    I doubt they’ll use the exact Erbitux sequence due to patent issues. This presentation is more of a proof of principle for the technology imo. We know they have their own EGFR antibodies…

    ohad

  27. Thanks for the article. You mention that arql is competing with at least 10 other c-MET inhibitors so does this mean arql is one of the most attractive of them? Also, you often adjust you positions in the biotech portfolio by buying some and selling others…what would you sell or add now?

    Also, BVF seems like they are taking some of their profits from arql…selling more than 3.7 million shares.

    Your opinions are apprciated.

  28. heymang,

    Looks like they want to at least have the opportunity to go all the way alone until completion of the pivotal ALL trial. I can certainly see the rationale there although I’d do a licensing deal to pursue the NHL and CLL markets.

    Ohad

  29. sam,

    yep, ARQ 197 is one of if not the best c-MET inhibitors out there. It’s always possible that some of the new inhibitors will perform better but most of the competition is rather early.
    I just posted a new article on ARQL following the results. At the end you can find the portfolio. We haven’t made any changes. I will definitely consider buying more ARQL after seeing results at ASCO.
    Can’t blame anyone who sells after seeing nice gains. I don’t know if they have other reasons or not.

    ohad

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