Corvus (“CRVS”) is advancing a potentially best in class anti-CD73 monoclonal antibody (mAb) in solid tumors and trades at a negative enterprise value. The adenosine target CD73 was recently validated in a large, well-controlled randomized Phase 2 clinical trial readout executed by Astrazeneca called The COAST Trial (COAST). Our thesis is Astrazeneca’s (AZN) COAST trial data validates CD73 in a meaningful way and Corvus is a significant beneficiary. The broader adenosine class continues to be validated by large pharma licensing deals. While CRVS’ anit-CD73 mAb called Mupadolimab (MUPA) should drive the bulk of company’s intrinsic value, there is an unappreciated pipeline including an ITK inhibitor (CPI-818), Ciforadenant an adenosine A2A receptor antagonist as well as a 46% ownership and board control of Angel Pharmaceuticals its Chinese subsidiary which is valued >$100M. Comparable companies with similar probabilities of success trade for significantly more CRVS has multiple assets which we believe will unlock shareholder value.
Mupadolimab and the ATP/Adenosine Axis
Various biotech companies are advancing therapies that block adenosine which is known to be immunosuppressive in the tumor microenvironment. Several targets involved in the pathway include CD39, CD73 and adenosine itself. Corvus’s lead asset is an anti-CD73 mAb called Mupadolimab. MUPA’s key differentiating feature versus other anti-CD73s is the dual property of CD73 blockade and ability to stimulate B-Cells. Antibodies modulating B-Cell function have been highly successful. MUPA greatly increases the expression of CD69, a marker of B-cell activation compared to Oleclumab, AZN’s anti-CD73 antibody. Despite the array of companies interrogating CD73, data had not provided strong supporting evidence until AZN’s COAST data proved highly statistically significant with a Progression Free Survival (PFS) Hazard Ratio of 0.44.
Astrazeneca COAST trial data for Oleclumab, its anti-CD73
At the ESMO conference in September 2021, Astrazeneca shared phenomenal data on its anti-CD73 Oleclumab (O). In a front-line randomized control trial of 127 patients with NSCLC study comparing AZN’s anti PD-L1 inhibitor Durvalumab (brand name Imfinzi) plus Oleclumab vs. Durvalumab (D) alone, the Oleclumab arm significantly outperformed. The confirmed Overall Response Rate (ORR) in the combo D+O arm was 30% vs. 17.9% in the mono D arm. The confirmed + unconfirmed ORR in the combo D+O arm was 38.3% vs 25.4% in the mono D arm. Further, the Progression Free Survival Hazard Ratio was 0.44 for the Oleclumab arm. There were no additional adverse events in the Oleclumab arm. This is incredible data for Oleclumab and AZN announced it is moving into a Phase 3 trial. Note, there is a third arm in COAST comparing Monalizumab (M), an NKG2A inhibitor not discussed in this write-up which also produced impressive results.
COAST ESMO Data
While the COAST data was fantastic on a stand-alone basis, bears have pointed to a perceived underperformance of the Durvalumab arm in COAST relative to its prior landmark PACIFIC trial Durvalumab arm. In PACIFIC the D arm had a PFS of 16.9 months vs. the D arm in COASTwhich had a PFS of 6.3 months. Cross trial comparisons are problematic as baseline characteristics and other factors do not match. Hence, the gold stand is a randomized controlled trial, which is exactly what we have in COAST. The COAST data should stand on its own. However, recognizing investors would flag this disparity AZN specifically addresses the question and AZN provided a data analysis comparing the subset of PACIFIC patients that match the baseline characteristics of patients in COAST. The analysis showed identical ORRs of 24.6% in each arm and PFS-10 month of 38% in COAST D and 44.6% in PACIFIC D. (see below). AZN strongly believes in the Oleclumab data and has gone out of its way to illustrate a match control, which we think impairs the bear case.
Mupadolimab to date
Corvus initially began to reflect AZN’s COAST data in its valuation as CRVS stock price moved from $2 to over $9 in weeks following the data release. Owing to poor communication around MUPA’s expectations and a treacherous biotech market, Corvus has round tripped all price gains and is back to the low $2s/share at the time of this writeup. Corvus presented early data for MUPA at SITC in November 2021 which disappointed the market for a few reasons:
Management had pointed to a 20% ORR bar for success. This guidance was both aggressive and not intended to be applied to the early Phase 1 data which was the subject of the SITC presentation. The actual SITC data showed some Stable Disease and tumor regression but no Partial Responses (see below). The point of the early phase 1 data is there was some signal of efficacy.
MUPA is being studied in PD-(L)1 experienced (failures) patients in HNSCC and NSCLC. The SITC MUPA data was median 4th line patients vs. Oleclumab in COAST, which was frontline checkpoint naïve. These are not remotely comparable patient populations. Later line therapy has a much lower bar for success in terms of response rates and survival. Investors failed to understand this.
Why the data should improve:
The pivotal trial will be run in frontline NSCSC like Oleclumab. Corvus has outlined the trial design for a P2/3 NSCLC MUPA+Pembro in Stage IV frontline checkpoint naïve patients, a patient population closer to COAST. The trial is expected to begin in 2022
Anti-CD73 therapies have shown efficacy in combo with PD-(L)1 checkpoints. Only 4 out of 16 patients shown in the SITC data had a PD-(L)1 checkpoint combined with MUPA.
MUPA expansion cohorts in PD-(L)1 experienced HNSCC and NSCLC will be combo PD-(L)1+MUPA and are beginning to enroll. This could provide more meaningful data in the target patient population with the correct dosing paradigm.
Data updates from the MUPA expansion cohorts will be coming in 2022
Competition in the anti-CD73 space is shown in the table below. For the moment, MUPA is second behind Oleclumab: