Welcome to a new issue of The Biopharma Report!
Regeneron and CytomX Announce Strategic Research Collaboration in the Field of Conditional Bispecific Therapeutics for the Treatment of Cancer
That’s a deal with a lot of synergy. CytomX’s Probody platform will be in perfect symbiosis with Regeneron’s Veloci-Bi bispecific antibody development platform.
The rationale behind the Probody platform is that the therapeutics are only activated (aka conditional activation) by proteases once they enter the tumor microenvironment in order to considerably limit off-target effects, increase the ability to better target tumors that don’t respond well to immunotherapy, and allow for more possible combos with lower toxicities.
The last 4 months were brutal for CytomX: first its lead asset praluzatamab ravtansine flopped in Phase II and then as usual 40% of the workforce was let go. The asset is not dead (yet?), but meaningfully advancing it in clinical development will require cash that CytomX doesn’t have - hence why further development will not be possible without a partner with deep pockets. It is important to note that this isn’t the first time praluzatamab disappointed - so there is possibly a trend here.
Investors obviously freaked out with the last data drop, but the Regeneron deal gave CytomX a nice - and much needed - boost.
CytomX’s platform has generated a lot of interest from large pharmas over the last years with companies like AbbVie, Amgen, BMS, Pfizer and Astellas striking deals with the biotech to develop novel therapeutics.
But these partnerships haven’t always been successful. In 2018, Pfizer cut its collaboration short with CytomX because after 5 years of preclinical development, none of the 3 programs in the deal had actually reached the clinic. In 2019, BMS also terminated 3 discovery programs with CytomX - but they are still working together on 2 other programs.
CytomX’s Probody platform is by all means innovative. But innovative is not necessarily synonymous with valuable. The amount of partnerships between CytomX and large pharmas certainly signal interest but in my view CytomX needs more solid data to truly validate its platform. CytomX’s upcoming catalyst, the Phase II readouts from the CX-2029 program (in partnership with AbbVie) should give us a better understanding of the clinical and commercial potential of the Probody platform.
Regeneron has lately been doing a lot of changes to its portfolio in its quest to become a force to be reckoned with in oncology.
Earlier this year, Regeneron acquired Checkmate Pharmaceuticals for $250M. Checkmate’s lead asset was vidutolimod which is a promising TLR9 agonist that is being studied - in combos - for melanoma, non-melanoma skin cancers, and head and neck cancer.
Later, in a very bold move, Regeneron acquired the worldwide rights to Libtayo - the drug it helped develop - for $900M from long-time partner Sanofi. From the get-go Regeneron was clear about the fact that it was gunning for combo opportunities for Libtayo. Regeneron was clearly shooting for the stars in terms of oncology.
Regeneron’s management is not naive, they know that to be the man, you need to beat the man - in other words, if they want to dominate the PD-1/PD-L1 market, they need to lock horns with Merck’s Keytruda and BMS’s Opdivo.
Libtayo as a monotherapy does not stack up well to Keytruda and Opdivo - which makes reaching blockbuster status an uphill battle. On the other hand, combining Libtayo with other therapeutics can unlock new opportunities - and here is where CytomX’s Probody technology can come in handy. The range of cancers that will be targeted by the Regeneron-CytomX alliance has not been disclosed but the list will probably overlap with the labels of Opdivo and Keytruda.
If CytomX can deliver with its Probody platform, Regeneron will have a sizable shot at significantly gaining more share in the oncology market. But Regeneron is not putting all of its eggs in one basket - especially given CytomX’s lack of clear track record - and is pursuing more assets to combine with Libtayo.
Merck to Acquire Imago BioSciences
In preparation for the post-Keytruda world, Merck has been ramping up acquisitions over the last 2 years, first with Acceleron, then VelosBio, and now Imago. All acquired assets are meant to strengthen Merck’s hematology portfolio in the long run.
LSD1 inhibition is an interesting mechanism with promising potential in myeloproliferative neoplasms. Imago’s asset, bomedemstat, is being tested in essential thrombocythemia, polycythemia vera, and myelofibrosis, with some data due to drop next month just before the ASH (American Society of Hematology) meeting. A Phase III study in essential thrombocythemia has already been discussed with the FDA and Imago is also getting ready for a Phase II study in polycythemia vera.
There is considerable commercial potential in these 3 indications.
The most attractive opportunity is arguably in essential thrombocythemia given how unattractive the available therapeutic options are: hydroxyurea which has been linked to a possible increase in risk of developing acute myelogenous leukemia and venous thrombosis, interferons that come with their fair share of side effects, and anagrelide which is probably the least effective of the three. In addition to that, 20% of patients on hydroxyurea develop some sort of intolerance or resistance to the compound - this will be the initial focus for bomedemstat since the target label is for second-line treatment.
Therapeutic options for polycythemia vera are to a degree similar to those in essential thrombocythemia: hydroxyurea and interferons, as well as chemo drug Busulfan and JAK inhibitor Jakafi from Incyte/Novartis. The market potential here is not as clear cut as for essential thrombocythemia, but Imago’s management seems to be optimistic about how fast the polycythemia vera market is growing.
The myelofibrosis opportunity is a tricky one. Imago’s rationale is that there is no disease modifying agent for myelofibrosis - which is true - but the battlefield is far from ideal. Merck’s asset will be competing with Incyte/Novartis’ Jakafi, BMS’ Inrebic, and CTI Biopharma’s Vonjo. All of these 3 drugs are JAK inhibitors. There are always some safety concerns with this class of drug - which could be a point of entry for Merck’s asset if the data is solid.
Merck’s soon-to-be newest asset bomedemstat is also being tested in combo with Jakafi and Tecentriq for myelofibrosis and small cell lung carcinoma (SCLC) respectively. Both of these programs are in Phase I.
Merck will not be the only player in the LSD1 inibitor space. BMS, Otsuka, Jubilant Therapeutics and Oryzon all have active LSD1 inhibitor programs in solid tumors and acute myeloid leukemia (AML). But the LSD1 inhibitor landscape has witnessed some setbacks recently.
In 2014 Roche had signed a $500M deal with Oryzon to develop an LSD1 inhibitor in AML and solid tumor, but in 2017, Roche terminated the alliance as a result of “internal portfolio reprioritization” - Oryzon is still developing the asset in AML, SCLC and neuroendocrine tumors. In 2020, Incyte killed its LSD1 inhibitor program spinning it as a “strategic business decision”.
But perhaps the most concerning aspect of LSD1 inhibitors is the safety side of things. GSK was developing its own LSD1 inhibitor in relapsed/refractory SCLC but terminated the program mid-Phase I because “the risk-benefit profile did not favor continuation” - which basically means that safety risks were just too great. Last month, Salarius paused its phase 1/2 trial of LSD1 inhibitor seclidemstat in sarcoma on safety grounds. There is not enough data to tell if this could be a class problem, but this is definitely something Merck is on the lookout for - especially if one of their selling points might be that they have a superior safety profile to JAK inhibitors. Upcoming data drops both from the bomedemstat programs as well as Oryzon’s LSD1 trials should provide additional insights in terms of safety for this drug class.
DISCLAIMER: This is for informational purposes only, you should not construe any such information or other material as legal, tax, investment, financial, or other advice.
DISCLOSURE: I have no business relationships with any company that is mentioned in this article.