Biotech General Discussion

Public·93 members

Back

manny.vacchiano

May 17, 2021

BPIQ Pro

Premium Analyst

CVM Data Still Months Away?

CVM's pending Phase 3 report out of its long term head & neck cancer study of its immuno-oncology reagent multikne (see image below for mechanism of action) is getting lots of attention, especially given the length of time of the study and that it is taking for data report-out. Today, STAT news/Adam Feuerstein published an article that is very negative on CVM and their current trial, which follows another STAT article from May 5, which discussed some of the negative history with CVM and this trial. Many of these issues were raised in a previous Seeking Alpha article. Regarding the latest accusations by STAT of CVM, it seems very possible that CVM does NOT have overall survival data yet, but they know that there is a reasonable chance that the trial will not hit its primary endpoint, but they are trying to convince investors that even some of the secondaries could be a win for them.

The intent of this post, or our accompanying much more extensive forum post on BPIQ.com, is NOT to defend CVM or STAT. As investors we are often caught in the middle of CEOs, who by their job description are excellent salespeople for their company. And journalists, who make a living on hyping up issues. The purpose of this post is to announce that we are pushing out our estimated date for data readout to July 31, 2021, and to provide more information regarding the timing of this readout and its likelihood of success. Keep in mind that our updated July 31, 2021 date is a very rough estimate date. It is mainly based on the fact that another long-term cancer trial in our database, with a data lock 2 months before CVM's Ph3 data lock, has not yet reported out.

The other very long-term cancer trial that is pending data readout, that we find in our database is the following: The NWBO Phase 3 trial for its cell therapeutic product - DCVax-L in glioblastoma (See IQ card HERE). We provide Table 1 below, where we compare that NWBO DCVax Ph3 trial to CVM's current Multikine Ph3 trial, but to another long-term cancer trial as well, Elevar's Apatinib in gastric cancer. As you can see from Table 1, the data lock for NWBO's trial was October 5, 2020 and it has not yet read out. CVM's data lock data was December 7, 2020. Thus, from a rough standpoint, CVM's trial might read out around 2 month's after NWBO's trial. It is noteworthy that another long-term cancer trial, Elevar's Angel trial of Apatnib in gastric cancer, had a top-line readout about 4.5 months after last patient event, and a full publication about 7.5 months after last patient event. The last patient event in the CVM trial was over 12 months ago, April 2020.

Regarding the likelihood of success of CMV's trial, we like to look at prior trial results (See Table 2). Of course, CVM's phase 3 trial has many more patients and sites (928/101 vs. 41-54/4) and has overall survival as its primary endpoint. The Multikine treatment in the trials seemed similar except that we did not find enough detail regarding the phase 3 regimen of cyclophsophamide, indomethacin and zinc to be certain those were delivered in the same way, and we didn't find a mention of cisplatin post-surgery in the phase 1 and 2 trials. There was some overall survival analysis done of CVM's phase 2 trial, but that used a cross-trial comparison to historical trials, a suspect analysis for which to base likelihood of success on a prospective, blinded clinical trial with an active standard of care control arm. Bulls point to the length of the CVM trial, which seems unexpectedly long given the survival rates of standard of care in this patient population. However, we do not know how much standard of care has improved since those trials that CVM used for their cross-trial comparison to get historical survival rates. Showing an overall survival benefit against and active standard of care is a pretty high hurdle without having any head-to-head comparative data from previous trials. Thus, for us, this seems to be a high risk trial in terms of extrapolating prior results to an increased survival rate, the phase 3 primary endpoint.

From an investment standpoint, we find way too many yellow/red flags on CVM and this trial to buy CVM stock or make any other bullish investment in this company. We have not made any negative bets (short or negative options plays) either. However, we find the prior issues with the FDA and IDMC concerning. There have been some serious accusations by the FDA that accompanied a clinical hold in 2016 (See footnote (FN) 1). Furthermore, there were some serious issues brought up by the Independent Data Monitoring Committee (IDMC) (See FN2). And we do not know the impact of issues with the former Clinical Research Organization involved in the Phase 3 trial that led to CVM's legal battle, where they alleged the CRO breached their contract with CVM and committed fraud (See THIS CVM SEC filing for more details). Finally, we find it very concerning that the company has no other drug candidate or ongoing trial, and apparently has not dosed a patient in this phase 3 trial in years.

See Full Table 1 (Click table below):

Table 2

FN1

FDA issues with CVM Ph3 Multikine study from 2016 letter to CVM (available here):

"In its partial clinical hold letter, FDA identified the following specific deficiencies: a) FDA stated that there is an unreasonable and significant risk of illness or injury to human subjects and cited among other things the absence of prompt reports by us to the FDA of IDMC recommendations to close the study entirely (made in spring of 2014) or at least to close it to accrual of new patients (made in spring of 2016); b) FDA stated that the investigator brochure is misleading, erroneous, and materially incomplete; and c) FDA stated that the plan or protocol is deficient in design to meet its stated objectives. In its partial clinical hold letter, FDA also identified the information needed to resolve these deficiencies. In addition, FDA’s partial clinical hold letter included two requests relating to quality information regarding our investigational final drug product, which were noted by FDA as non-hold issues.

FN2

IDMC issues with CVM Ph3 Multikine study (available here):

"although on two occasions the IDMC has issued recommendations that would have closed the study entirely (spring of 2014) or at least closed it to accrual of new patients (spring of 2016)."

Table 1 references

1 https://www.clinicaltrials.gov/ct2/show/study/NCT01265849?term=multikine&rank=3

2 https://cel-sci.com/wp-content/uploads/2020/06/Scientific_Multikine_Presentation_061020.pdf

3 https://www.businesswire.com/news/home/20201207005262/en/CEL-SCI-Announces-Update-on-Phase-3-Cancer-Trial-Results

4 https://www.clinicaltrials.gov/ct2/show/study/NCT00045968?term=DCVax&show_locs=Y

5 https://nwbio.com/northwest-biotherapeutics-announces-completion-of-phase-3-trial-sites-databases/

6 https://nwbio.com/northwest-biotherapeutics-announces-data-lock-of-phase-iii-trial/

7 https://clinicaltrials.gov/ct2/show/study/NCT03042611

8 LSKB Announces that the ANGEL Study Has Reached its Primary Completion Date – Elevar Therapeutics

9 https://elevartherapeutics.com/2019/06/27/lsk-biopharma-announces-preliminary-review-of-top-line-results-from-angel-study-2/

10 Elevar Announces Results from the ANGEL trial, a study of Monotherapy Rivoceranib (Apatinib) in Late-Stage Gastric Cancer Patients – Elevar Therapeutics

Table 2 references