Takeaways from #Management Follow-up
$GSK has decided to return the rights to the SPEAR T-cell programs to ADAP. We understand from ADAP management that GSK's decision is likely due to a strategic shift away from cell therapy, rather than data driven. Overall, we think this development is neutral in its implication for ADAP, for the following reasons.
We view the opportunity for ADAP to gain full control to PRAME TCR as positive, because this target has recently been validated clinically by others (using the TCR T-cell approach or the related approach of TCR x anti-CD3 bispecific protein), but at the same time we note that ADAP's PRAME program is still in preclinical stage (IND 2023) andinitial clinical data remain up to 2 years away.
For the return of NY-ESO-1 TCR, although the GSK-developed sarcoma programs could supplement ADAP's MAGE-A4 TCR program (e.g. by addressing the MAGE-A4 negative synovial sarcoma cases or expanding to the MRCLS indication), we think the incremental benefit has to be weighed against the increased development costs especially in the setting of limited cash runway.
Lastly, we note that GSK's decision is unlikely driven by anything intrinsic to the NY-ESO-1 sarcoma program, and that it could be a result of an overall strategic shift or it could be related to a recent update from an NY-ESO-1 study in NSCLC, a more meaningful indication for the pharma company, where the anticipated level of clinical activity was not observed.
Management Follow-Up
Adaptimmune Therapeutics (ADAP) today announced that GSK is to return the rights to the NY-ESO program and the PRAME program, and that negotiations on the terms of the transfer are to be completed by YE22. With the termination of the license agreement, GSK is to cease to have any rights to nominate any additional targets. ADAP noted that it is to continue to prioritize and focus on its lead MAGE-A4 franchise while determining the development path for the complementary PRAME and NY-ESO assets.
When asked why GSK decided to return the programs, ADAP noted that GSK’s decision-making was not data driven, and that GSK also terminated its collaboration with Lyell Immunopharma (a collaboration set up to develop new technologies to improve cell therapies), suggesting that GSK's decision might reflect a strategic decision to move away from cell therapy.
With focus on the NY-ESO-1 (lete-cel) program, ADAP shared that GSK expects to complete the potentially registrational phase 2 IGNYTE-ESO study for synovial sarcoma (SS) and myxoid/round cell liposarcoma (MRCLS) in mid-2023, with final readouts in late 2023. Importantly, ADAP noted that GSK is expected to fund the study through completion.
Recall, ADAP also has a wholly owned afami-cel (ADP-A2M4) program for synovial sarcoma, with BLA filing remaining on track for 4Q22.
Synergy between afami-cel and NY-ESO-1 in synovial sarcoma. ADAP shared that it anticipates to build a focused commercial footprint to deliver afami-cel to synovial sarcoma patients, noting that this commercial footprint would be almost identical to the commercial footprint for NY-ESO-1.
The company elaborated that, based on its research, among synovial sarcoma patients, ~70% are MAGE-A4+ and ~70% are NY-ESO-1+. ADAP shared that it has not tested both antigens in the same patient population but noted that one potential scenario might be that ~50% of synovial sarcoma patients could be double-positive and ~20% of patients could be single-positive.
Next step for NY-ESO-1. ADAP considers it attractive to put NY-ESO-1 through the same commercial footprint given the relatively limited extra cost, but noting that the final decision is to be data-driven. The company additionally highlighted that NY-ESO-1 is also being evaluated in MRCLS patients.
With focus on the PRAME program, ADAP shared that it is currently developing the program preclinically (not yet transitioned to GSK), and that it expects to file the IND for the program in 2023.
When asked about the differentiation of the company’s PRAME program from others in the field, ADAP highlighted: (1) the company’s ability in generating differentiated TCR with high quality; and (2) its manufacturing process that can epigenetically modify the cells and generate a youthful and undifferentiated phenotype.
Of note, competitor Immatics (IMTX) earlier this month reported updated data from its phase 1a and 1b studies of PRAME targeting TCR-T cells, IMA203, in patient with r/r solid tumors. The data demonstrated that, in patients treated with =1E9 infused TCR-T cells across phase 1a and 1b, 50% (6/12) ORR was observed. In phase 1b (improved manufacturing; excluded heavily pre-treated patients), 80% (4/5) ORR was reported.
In terms of manufacturing, ADAP shared that the manufacturing adopted by GSK for NY-ESO-1 is different from the company’s manufacturing process when developing the product (prior to transition to GSK in 2018), but noted that the company has no problem running multiple manufacturing processes.
Cash runway. ADAP shared that, given it has not made any decisions on the next steps for NY-ESO-1, the company is not revising its cash runway guidance. Recall, the company in 2Q22 update noted that its quarter-end cash and equivalents of $97.8MM, included in total liquidity of $258.1MM, would be sufficient to fund operations into early 2024.
Recap of the Collaboration and License Agreement between ADAP and GSK. The companies in June 2014 announced their strategic collaboration and license agreement for up to 5 programs including NY-ESO. In September 2017, GSK exercised its option to exclusively license the right to research, develop, and commercialize NY-ESO SPEAR T-cell therapy program. Since then, two additional targets, including PRAME, were nominated as collaboration program targets. Under the terms of the agreement, ADAP was eligible to receive commercialization milestones and mid-single- to low-double-digit royalties on worldwide net sales.