PFE - Caribou Biosciences: Positive CB-010 Data Leads To First Half 2024 Catalyst

2023-07-17 05:11:51 ET

Summary

• Caribou Biosciences' results from the dose expansion portion of the phase 1 ANTLER study, using CB-010 for the treatment of patients with relapsed/refractory second-line LBCL patients, are expected in the 1st half of 2024.
• A $25 million equity investment from Pfizer was achieved.
• Dose escalation updates to be released from ongoing open-label phase 1 CaMMouflage study as it progresses; This study is using CB-011 for the treatment of patients with r/r MM.
• CB-012 is an allogeneic anti-CLL-1 CAR-T cell therapy for the treatment of patients with relapsed or refractory acute myeloid leukemia; to use both immune cloaking and PD-1 knockout mechanisms.

Caribou Biosciences ( CRBU ) has made great progress lately relating to its advancement of its pipeline. The reason why I state that is because it was able to receive a $25 million equity investment from Pfizer ( PFE ). With this equity investment, it will use the proceeds to advance CB-011, which is being developed as an immune-cloaking allogeneic anti-BCMA CAR-T cell therapy for the treatment of patients with multiple myeloma [MM]. Besides that, it also just recently reported positive results from its phase 1 ANTLER study, which tested its allogeneic anti-CD19 CAR-T cell therapy CB-010 for use in patients with relapsed/refractory B-cell non-Hodgkin lymphoma [r/r B-NHL].

The next plan is to enroll patients into the phase 1 dose escalation portion of this study, which is to determine the recommended phase 2 dose [RP2D] of CB-010 for second-line patients with large B-cell lymphoma [LBCL]. Plus, it had established two firsts as well with respect to this therapy, which I will be going over below. Despite the release of positive results from this phase 1 study, there is another catalyst that investors can look forward to from this program. It is expected that results from the dose escalation portion of this study, using CB-010 for the treatment of second-line LBCLC patients, will be released by the 1st half of 2024. Not only all of these advancements, but the company is now well capitalized to advance its pipeline going forward. That's because it announced the pricing of an upsized offering of $125 million. Such an offering is expected to close on or about July 18, 2023, subject to satisfaction of customary closing conditions.

Positive Results From ANTLER Study Allows Advancement Into Dose Expansion Portion

As I stated above, Caribou Biosciences released positive long-term follow up data from the dose escalation portion of its ongoing phase 1 ANTLER study. This portion of the study used CB-010 for the treatment of patients with relapsed or refractory B cell non-Hodgkin lymphoma [r/r B-NHL]. One important thing to note is that CB-010 is an allogeneic anti-CD19 CAR-T cell therapy. This is one of the firsts I talked about before, in that it is the first allogeneic anti-CD19 CAR-T to be evaluated in second-line large B-cell lymphoma [LBCL] patients. The second first, is that it is the first allogeneic anti-CD19 CAR-T cell therapy in the clinic with a PD-1 knockout effect. What does this PD-1 knockout mean? It is a genome-editing strategy that is deployed to limit premature CAR-T cell exhaustion, which in turn might possibly allow for enhanced antitumor activity.

The phase 1 ANTLER study tested three dose levels of CB-010, which were evaluated in patients with multiple subtypes of aggressive r/r B-NHL. Such doses of CB-010 that were tested for these patients were as follows:

• 40x10 ⁶
• 80x10 ⁶
• 120x10 ⁶

It was noted that with respect to the overall r/r B-NHL population who only took a single dose of CB-010, there was a 94% overall response rate [15 out of 16 patients responding]. The complete response [CR] rate was 69% [11 out of 16 patients]. This is pretty good and then such clinical data was evaluated further in terms of only patients with Large B-cell lymphoma [10 patients]. A 90% [9 out of 10] ORR and 70% [7 out of 10] CR was observed for this patient population.

Investors might be able to benefit here with respect to the advancement of this phase 1 ANTLER study, because of a catalyst opportunity. It is expected that Caribou will release dose expansion data from this phase 1 trial in the 1st half of 2024. The goal for the dose expansion portion of the study is to evaluate use of CB-010 second-line LBCL patients. The main goal for this program is to develop an "off the shelf" therapy which can be used for LBCL patients who are either not eligible to receive 1st-line SOC therapy or who can't afford to wait for Autologous CAR-T. Even when only looking at the 4 second-line LBCL patients who were given one dose of CB-010, the data was good. It was noted that the overall response rate [ORR] for these patients was 100% [4 out of 4 patients] and the complete response rate was 50% [2 out of 2 patients]. The dose expansion data is which is expected to be released in the 1st half of 2024 should shed more light on the use of CB-010 for these second-line LBCL patients.

Financials

According to the 10-Q SEC Filing , Caribou Biosciences had cash, cash equivalents and marketable securities of $291 million as of March 31, 2023. It believed that it would have enough cash to fund its operations into 2025, but despite this cash runway there were two recent cash raising events. The first financial activity was a $25 million investment from Pfizer. Pfizer purchased 4,690,431 common shares of Caribou's stock at a price of $5.33 per share. While this was a good way to obtain non-dilutive cash, the biotech still chose to raise additional cash after this event anyways.

It enacted an upsized underwritten public offering of 19,230,769 shares of its common stock at a public offering price of $6.50 per share. Before deducting expenses, it is expected that Caribou will receive approximately $125 million in gross proceeds from it . In addition, this company also offered the underwriters a 30-day option to purchase up to an additional 2,884,615 shares of its common stock at the public offering price. It is expected that this offering will close on or about July 18, 2023, subject to satisfaction of customary closing conditions.

Risks To Business

There are several risks that investors should be aware of before investing in Caribou Biosciences. The first risk to consider would be with respect to the ongoing advancement of the phase 1 ANTLER study, which is using CB-010 for the treatment of patients with r/r B-cell lymphomas. That's because the dose expansion portion of this study is going to specifically look at treating second-line large B-cell lymphoma [LBCL] patients. While preliminary ORR data looked good for second-line LBCL patients [ORR of 100% - 4 patients], there is no guarantee that dose expansion data to be released in the 1st half of 2024 will end up being similar. A second risk to consider would be the advancement of CB-011, which is being advanced in the ongoing open-label CaMMouflage phase 1 study . This early-stage study is using this immune-cloaking allogeneic anti-BCMA CAR-T cell therapy for the treatment of patients with relapsed or refractory multiple myeloma [r/r MM].

It is expected that Caribou will release updated data as thus study progresses over time. Once such data is released there is no assurance that positive data will be released from it, or that it will continue on to the next dose level [currently being advanced at dose level 1]. The third and final risk to consider would be with respect to the $25 million equity investment from Pfizer. While the big pharma company likes what it sees thus far with respect to clinical data, there is no guarantee that it won't change its mind later on. Especially, if the dose expansion data for CB-010 or other programs don't progress well in clinical testing. At such point, Pfizer won't hesitate to sell its shares of the Caribou.

Conclusion

Caribou Biosciences has two programs being advanced in phase 1 testing. These would be with respect to the advancements of CB-010 for the treatment of patients with second-line LBCL and CB-011 for the treatment of patients with r/r multiple myeloma. The phase 1 ANTLER study, using CB-010 for second-line LBCL patients, is the program which is the furthest along. The next set of data to be release from this ANTLER study is expected by the 1st half of 2024. There are a few other catalysts which investors can look forward to as well. The first is the phase 1 CaMMouflage study, which is using CB-011 for the treatment of patients with r/r MM.

Results from this study are expected to be released as it progresses, since it is an open-label study. What separates CB-011 from the other candidate CB-010, is that it has a different mechanism of action. The following differences to be noted are as follows:

• CB-010 - "off the shelf" allogeneic CAR-T with checkpoint disruption using the editing of a PD-1 knockout - Effectively to limit premature CAR-T cell exhaustion [CAR-T effect dropping off], which in theory should improve anti-tumor activity
• CB-011 - "off the shelf" allogeneic CAR-T with immune cloaking using editing of B2M KO, B2M-HLA-E insertion, which in theory shields CAR-T from immune system rejection

As I stated before, the CB-011 CAR-T is being used for cloaking. That is, to cloak the CAR-T from being rejected by the patients' immune system [Blunt the rejection of both T-cells and natural killer cells]. Lastly, the biotech is moving forward with another candidate in its pipeline. It is advancing the use of CB-012 for the treatment of patients with r/r Acute myeloid leukemia [AML].

An IND application filing, to eventually begin a phase 1 study for this indication, is expected by the 2nd half of 2023. Think of CB-012 as effectively having the mechanism of action of both CB-010 and CB-011 together at the same time. That is, to have both the immune cloaking and PD-1 knockout effects of both in one CAR-T. With positive clinical data from the dose escalation portion of the phase 1 ANLTER study using CB-010 for the treatment of patients with r/r B-cell lymphoma, plus dose expansion data from the same study for r/r second-line LBCL patients expected in the 1st half of 2024, I believe that investors might be able to capitalize on any possible gains made.

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