2023-08-29 00:15:03 ET
Summary
- Compass Therapeutics is developing antibody therapies for cancers, with their lead candidate being CTX-009, a dual inhibitor of VEGF-A and DLL4.
- The company has upcoming topline data from their colorectal cancer and biliary tract cancer programs, as well as a CD137-PD1 combo phase 1b study.
- Phase 1a/1b dose escalation data from CTX-009 showed promising results in solid tumors, with a 13.6% overall response rate in the higher dose cohort.
Compass Therapeutics ( CMPX ) develops various antibody therapies for cancers. Lead candidate is CTX-009, a dual DLL4 x VEGF-A inhibitor that originated with ABL Bio of South Korea. It is an angiogenesis inhibitor, meaning it inhibits both VEGF and DLL4, which may stop angiogenesis (blood vessel formation in tumors, essential for tumor survival and growth), while remaining unhindered by multi-VEGF resistance.
Here’s the pipeline:
Nearest catalyst according to this is topline colorectal cancer data from CTX-009 in H2 2023, which is now. Next year, we have topline data from the biliary tract cancer program. There’s a second program, CTX-471, which targets CD137 and will have topline data in Q4 from a CD137 - PD1 combo phase 1b study.
Colorectal cancer is a devastating disease. I checked out tickerbay.com to get some details about prevalence and market potential, approved and pipeline drugs and so on. According to them:
In terms of market size, the global colorectal cancer market was valued at approximately $8.4 billion in 2020 and is projected to reach $11.9 billion by 2027, growing at a compound annual growth rate (CAGR') of around 5.2% during the forecast period. The market growth is driven by factors such as increasing incidence, advancements in treatment options, and the introduction of novel therapies.
They also list a number of approved drugs - chemotherapy, targeted therapies and immunotherapies are the non-surgical options. A detailed discussion is available here . The point is, there is always space for a drug with a different mechanism of action.
In 2021, just as Compass was signing its deal with ABL, the two companies presented phase 1a/1b dose escalation data from CTX-009 (then called ABL001) as a monotherapy in solid tumors. This trial was done in South Korea and was sponsored by ABL. Data showed that there were no dose limiting toxicities at any cohorts, and the only grade 3 adverse event was hypertension. A few others, like anemia and proteinuria, were grade 1 or 2, and were easily managed.
In terms of efficacy data, at the higher dose cohort, there were 3 PRs, 11 SDs and 8 PDs, giving an ORR of 13.6% and a DCR of 63.6%. At the lower dose cohort, there were no CRs or PRs, so ORR was 0%, however there were 10 SDs and 7 PDs, giving a DCR of 58.8%. Two of CRC patients saw response durations of 300 days. CRC was, by far, the most successful indication.
Exposure to prior VEGF inhibitors did not improve results, however, interestingly, such exposure raised the profile of the data from the lower dose cohort. Here, we now saw 3 PRs, 12 SDs and 9 PDs, while there were no PRs in the higher dose cohort.
Also interestingly, ORR was much better in DLL4 expressing patients. However, gastric cancer patients with DLL4 expression did remarkably better compared to GC patients who were DLL4 negative. The results could have been skewed by the fact that there were too few patients in the DLL4 negative arms.
To be noted, there was a confirmed partial response in a female gastric cancer patient with four prior lines of therapy and had a duration of 12 weeks. There was a similar confirmed PR in another female CRC patient, who also had four prior lines of therapies, that also lasted 12 weeks.
In 2021, combo trial with chemo was ongoing. In 2023, from such a phase 1b trial, durable responses were seen in patients with cholangiocarcinoma for CTX -009 in combination with paclitaxel. In all of these phase 1 trials, there were 8 PRs, 6 confirmed by RECIST in 33 advanced solid tumor patients treated.
There is data available from a South Korean trial with paclitaxel combo in BTC patients. Across multiple BTC subclasses, there were 9 confirmed PRs, with between 33% and 57% tumor reduction. Also, this time, the number of days between C1D1 and EOT (cycle 1 day 1 and end of treatment) were much longer, at 580 days at the highest. Overall survival was 12.5 months while duration of response was 6.9 months.
The adverse event profile here was informed by those of bevacizumab and paclitaxel, and was a little poorer than monotherapy. However, some of the SAEs can well be accounted for by these other two treatments. Treatment emergent adverse events related discontinuations were caused by confusion, embolism, pneumonia (grade 5), biliary fistula, large intestine perforation, blood creatinine increased, and blood urea nitrogen increased. As we can see, there was a TEAE-related death from pneumonia, possibly ascribable to chemo.
The company presented a comparison chart between this trial and other BTC trial data:
Parameter | CTX-009 | Mixed 2L and 3L | FOLFOX (ABC-06) 1 | Only 2L | Gem/Cis 2 | 1L | Gem/Cis + Durv 3 | Only 1L |
N | 24 | N=24 | 81 | N=81 | 204 | N=204 | 341 | N=341 |
ORR (%) | 37.5 | 64 (2L); 15 (3L) | 5 | 26 | 26.7 | 5 | ||
OS (months) | 12.5 | 6.2 | 11.7 | 12.9 | 12.5 | |||
PFS (months) | 9.4 | 4.0 | 8.0 | 7.2 | 9.4 | |||
Any AE (%) | 100 | 99 | 55 | 99.4 | ||||
Gr 3/4 AEs (%) | 92 | 60 | 71 | 74 | ||||
Deaths (%) | 1 (4%) | 10 (12%) | 17 (8%) | 13 (4%) | ||||
AEs leading to | ||||||||
discontinuation (%) | 25 | ~ 12 | 10 | 13 |
Financials
CMPX has a market cap of $308mn and a cash balance of $169mn. R&D expenses were $10.2 million for the quarter ended June 30, 2023, while G&A expenses were $3.1 million. At that rate, the company has a cash runway of 10-12 quarters.
The company is majorly held by institutions, with a 16% retail presence. Keyholders are Orbimed and Commander Aggregator. Orbimed is the primary funder, and management and Chairman are from Orbimed.
Risks
CMPX is effectively trying to validate data they had seen in the Korean trials, here in the US. These things are iffy, because, first, these are different populations with varying healthcare standards, and two, some of the data is not so strong.
Bottomline
CMPX has a number of major catalysts in the next 12 months, and prices are near 52-week lows. Cash balance is good, and prior data from Korea is compelling enough. I will continue watching CMPX for now.
For further details see:
Compass Therapeutics: South Korean Data Is Compelling, But Needs To Be Tested In The U.S.