On March 9, 2023 Gritstone bio, Inc. (Nasdaq: GRTS), a clinical-stage biotechnology company working to develop the world’s most potent vaccines, reported financial results for the fourth quarter and full year ended December 31, 2022, and provided recent clinical and corporate updates (Press release, Gritstone Bio, MAR 9, 2023, View Source [SID1234628439]).

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"In 2022, we presented positive Phase 1 or 2 data across our GRANITE, SLATE and CORAL vaccine programs, highlighting our ability to generate potent and durable immune responses in both cancer and infectious diseases," said Andrew Allen, M.D., Ph.D., Co-founder, President, and Chief Executive Officer of Gritstone bio. "Of greatest potential importance within our cancer vaccine programs, GRANITE and SLATE, is the consistent association between vaccine-elicited molecular responses in patients with prolonged overall survival. Also of note, we have demonstrated the ability of our therapies to turn "cold" tumors into "hot" ones – even in tough settings such as third line MSS-CRC. The positive results seen in these studies in treatment-refractory disease, coupled with consistent generation of neoantigen-specific cytotoxic T cells, underline the potential of our antigen prediction and heterologous prime-boost vectors (adenovirus and samRNA) to drive clinically important and differentiated immune responses. The clear next step is to move upstream and test the approach in newly diagnosed metastatic cancer patients, and this is well underway in a randomized Phase 2/3 trial with GRANITE in MSS-CRC."

Dr. Allen continued, "In 2023, we have several important milestones, most notably, the preliminary Phase 2 data from our Phase 2/3 GRANITE study in frontline MSS-CRC by year-end. We also plan to initiate a new, randomized Phase 2 trial of a KRAS-directed SLATE in patients with newly-diagnosed metastatic cancer in the second half of the year. We are highly encouraged by the data from our GRANITE program to date and believe success with our Phase 2/3 GRANITE study would support expanded evaluation across both cold and hot tumors and into different treatment settings including adjuvant therapy. This is an important year for personalized cancer vaccines, with multiple companies reporting randomized trial data, and a positive outcome in our trial in metastatic CRC, a clearly "cold" tumor, would be of huge significance, potentially opening the door for the majority of solid tumor patients to derive benefit from immunotherapy for the first time. Fueled by the extended survival and promising patient outcomes observed in our Phase 1/2 in advanced CRC, which are published in Nature Medicine, we confidently await our randomized Phase 2 data late this year."

Clinical Program Updates
Tumor-Specific Neoantigen (TSNA) Oncology Programs
GRANITE – Individualized, TSNA-directed vaccine-based immunotherapy
SLATE – "Off-the-shelf" shared TSNA-directed vaccine-based immunotherapy

Preliminary data from the randomized Phase 2/3 study evaluating GRANITE (individualized neoantigen vaccine for microsatellite-stable colorectal cancer [MSS-CRC]) remain expected in 4Q 2023.
— Enrollment of the Phase 2 portion of study, designed to evaluate the individualized neoantigen vaccine as a maintenance therapy in eighty patients with first-line MSS-CRC, is ongoing.

— The company remains on track to report preliminary data from the Phase 2 portion of the study, molecular response (circulating tumor DNA [ctDNA]) and progression-free survival data [evaluated by both RECIST and iRECIST criteria] on patients completing at least 4 months of treatment, in 4Q 2023.

Positive results from Phase 1/2 studies of GRANITE and SLATE reinforce association between molecular response (reduction in ctDNA level) and extended overall survival.

GRANITE
— In August 2022, interim results from the Phase 1/2 trial of GRANITE, Gritstone’s individualized neoantigen vaccine for solid tumor cancers, were published in Nature Medicine (here). The paper describes how Gritstone’s neoantigen-directed dual vaccination approach (referred to as "prime-boost") led to both priming and boosting of tumor-specific cytotoxic T cells, with associated molecular responses in approximately half of treated advanced colorectal cancer (CRC) patients.

— In November 2022, Gritstone announced the median overall survival (mOS) among molecular responders living with third line MSS-CRC (a subset within the Phase 1/2 study of GRANITE) will exceed 22 months; median not yet reached (here). This compares to mOS of 7.8 months in evaluable MSS-CRC patients in the study who did not exhibit a molecular response, and mOS of 6-7 months observed in pivotal studies of FDA-approved therapeutics in this context (trifluridine/tipiracil combination and regorafenib monotherapy). Molecular response rate (MRR) among evaluable MSS-CRC patients was 55% (6/11).

SLATE
— In September 2022, initial results shared at ESMO (Free ESMO Whitepaper) from Phase 1/2 study of KRAS-directed SLATE demonstrated similar molecular response rate and overall survival trend (here). In 38 patients with advanced solid tumors (largely MSS-CRC and NSCLC), SLATE v1 (n =26) and SLATE-KRAS (n=12) demonstrated a 39% MRR in evaluable patients with MSS-CRC and NSCLC. In 18 patients with NSCLC, all of whom had progress on prior (chemo)immunotherapy, a molecular response was correlated with extended OS. NSCLC patients with a molecular response demonstrated a median OS (9.6 months) more than double of those without a molecular response (4.5 months).
Infectious Disease Programs
CORAL – Second-generation SARS-CoV-2 vaccine program that serves as proof-of-concept for Gritstone’s infectious disease approach and the potential application of samRNA in infectious diseases.

Phase 1 CORAL studies continue, with enrollment in CORAL-CEPI trial (n = 341) now complete. Additional data from the CORAL-BOOST and CORAL-CEPI trials, which aim to further characterize and demonstrate the potential utility of self-amplifying mRNA (samRNA), are expected in 2Q2023.
— In August 2022, Gritstone reported 6-month neutralizing antibody data from the first two cohorts of its CORAL-BOOST trial. Results showed in all observable patients, the strong neutralizing antibody responses originally reported in January 2022 persisted without decay after 6 months (here).

— In October 2022, Gritstone shared interim positive results from the ongoing Phase 1 CORAL-BOOST and CORAL-CEPI studies at a Company-sponsored webinar. Collectively, these results showed Gritstone’s samRNA vaccine candidates to be well-tolerated and capable of driving strong, potentially durable and broad immunogenicity across several subject populations and settings.

— Enrollment in the CORAL-NIH trial completed in 2022. This study is sponsored and executed by the National Institute of Allergy and Infectious Disease (NIAID).
HIV – Collaboration with Gilead Sciences, Inc. (Gilead) under Gilead’s HIV Cure Program to research and develop vaccine-based HIV immunotherapy treatment.

The collaboration with Gilead Sciences, Inc. (Gilead) to research and develop a vaccine-based HIV immunotherapy treatment remains active and ongoing.
Recent Corporate Updates

In October 2022, Gritstone raised $45 million through a private investment in public equity financing to support development of its ongoing and future pre-clinical and clinical programs.

In February 2023, Gritstone announced a clinical trial agreement with the National Cancer Institute (NCI) to evaluate an autologous T cell therapy expressing a T cell receptor targeting mutated KRAS in combination with Gritstone’s KRAS-directed vaccine candidate, SLATE-KRAS, in a Phase 1 study led by Steven A. Rosenberg, M.D., Ph.D.

In February 2023, results from a preclinical study conducted in collaboration with Gilead Sciences were presented at Conference on Retroviruses and Opportunistic Infections (CROI) 2023. The first data disclosed from the Gritstone-Gilead HIV Cure collaboration, results showed that simian immunodeficiency virus (SIV) Chimpanzee Adenovirus (ChAd) and self-amplifying mRNA (samRNA) vaccines induced a strong and broad CD8+ T cell immune response, which was significantly enhanced in combination with immune modulators.
Intellectual Property Update
Gritstone’s IP estate includes issued patents related to its processes and technologies, including Gritstone EDGE, the company’s novel epitope discovery platform used in neoantigen prediction for its personalized cancer vaccines.

In December 2022, Gritstone announced the United States Patent and Trademark Office (USPTO) issued two new patents related to the company’s novel self-amplifying mRNA (samRNA) vaccine platform technology (U.S. Patent No. 11,504,421 and U.S. Patent No. 11,510,973).

In February 2023, the USPTO issued a separate patent (U.S. Patent No. 11,264,117) directed to Gritstone’s proprietary ChAd vector, which is modified to improve viral production.
Full Year 2022 Financial Results

Cash, cash equivalents, marketable securities and restricted cash were $185.2 million as of December 31, 2022, compared to $223.5 million as of December 31, 2021.

Research and development expenses were $111.4 million for the year ended December 31, 2022 compared to $97.5 million for the year ended December 31, 2021. The increase was primarily due to increases in personnel-related costs and clinical trial expenses.

General and administrative expenses were $29.0 million for the year ended December 31, 2022 compared to $25.9 million for the year ended December 31, 2021. The increase was primarily attributable to an increase in personnel-related costs and an increase in outside services for legal, finance, recruiting and other professional services to support our ongoing operations.

Collaboration, license, and grant revenues were $19.9 million for the year ended December 31, 2022, compared to $48.2 million for the prior year. During the year ended December 31, 2022, we recorded $1.6 million in collaboration revenue related to the Gilead Collaboration Agreement, and $7.7 million in collaboration revenue related to the 2seventy bio Agreement. During the year ended December 31, 2022, we recorded $9.5 million in grant revenue related to the CEPI Agreement and $1.2 million in grant revenue related to the Gates Agreement.
Conference Call and Webcast Details
A conference call and webcast to discuss fourth quarter and full year 2022 results will be held at 4:30pm ET today (March 9):

Conference call: 1-877-407-4018
Conference ID: 13734754
Webcast: View Source;tp_key=44c4441022

An archived replay will be accessible at View Source for 30 days following the event.

On March 9, 2023 CymaBay Therapeutics, Inc. (NASDAQ: CBAY), a clinical-stage biopharmaceutical company focused on developing therapies for liver and other chronic diseases with high unmet need, reported that it will host a conference call and live audio webcast on Thursday, March 16, 2023 at 4:30 p.m. Eastern Time to discuss financial results for the fourth quarter and year ended December 31, 2022 and to provide a business update (Press release, CymaBay Therapeutics, MAR 9, 2023, View Source [SID1234628438]).

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Conference Call Details
To access the live conference call, please dial 877-407-0784 from the U.S. and Canada, or 201-689-8560 internationally, Conference ID # 13736281. To access the live and subsequently archived webcast of the conference call, go to the Investors section of the company’s website at View Source

On March 9, 2023 Caribou Biosciences, Inc. (Nasdaq: CRBU), a leading clinical-stage CRISPR genome-editing biopharmaceutical company, reported financial results for the fourth quarter and full year 2022 and reviewed recent pipeline progress (Press release, Caribou Biosciences, MAR 9, 2023, View Source [SID1234628437]).

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"We successfully demonstrated the potential of our chRDNA genome-editing technology with promising clinical data from CB-010, our lead allogeneic cell therapy," said Rachel Haurwitz, PhD, Caribou’s president and chief executive officer. "The initial dose level of CB-010 demonstrated 6-month complete response rates that have the potential to rival the responses seen with approved autologous CAR-T cell therapies. We are excited that the FDA granted the CB-010 program RMAT and Fast Track designations last year. Our team drove additional pipeline progress with an IND clearance for CB-011, enabling us to activate clinical sites for our CaMMouflage Phase 1 trial. In 2023, Caribou plans to maintain this momentum by advancing two ongoing clinical trials for our off-the-shelf cell therapies in patients with hematologic malignancies and preparing an IND submission for our third program, CB-012."
Accomplishments and Highlights
Pipeline and Technology
•CB-010: Caribou reported promising data at dose level 1 (40×106 CAR-T cells) from its ongoing ANTLER Phase 1 clinical trial of CB-010 in patients with relapsed or refractory B cell non-Hodgkin lymphoma (r/r B-NHL).
◦Following a single infusion of CB-010 at dose level 1, all 6 patients in cohort 1 achieved complete responses as their best response. 3 of 6 patients maintained complete responses at 6 months, with 2 of 6 maintaining complete responses at 12 months. Caribou plans to provide an update from the ongoing ANTLER Phase 1 trial for CB-010 in H2 2023.
◦Clinical data presentations are available on Caribou’s website under Scientific Publications (www.cariboubio.com/technology/#pubs).
◦Following demonstration of an encouraging safety profile at dose level 2 (80×106 CAR-T cells), with no dose-limiting toxicities (DLTs) in the 3 patients treated, Caribou continues to enroll patients at dose level 3 (120×106 CAR-T cells).
◦The U.S. Food and Drug Administration (FDA) has granted CB-010 Regenerative Medicine Advanced Therapy (RMAT), Fast Track, and Orphan Drug designations. These

designations provide important benefits in the drug development process and are designed to facilitate and expedite development and regulatory review, including providing eligibility for priority and rolling reviews and accelerated approval, if relevant criteria are satisfied.
◦CB-010 is the first allogeneic anti-CD19 CAR-T cell therapy in the clinic, to Caribou’s knowledge, with a PD-1 knockout (KO), a genome-editing strategy designed to improve antitumor activity by limiting premature CAR-T cell exhaustion.
◦Additional information on the ANTLER trial (NCT04637763) can be found at clinicaltrials.gov (View Source).
•CB-011: Caribou recently activated clinical sites for the recruitment of patients at dose level 1 (50×106 CAR-T cells) of CB-011 in the CaMMouflage Phase 1 trial for relapsed or refractory multiple myeloma (r/r MM).
◦CB-011 is the first allogeneic CAR-T cell therapy in the clinic, to Caribou’s knowledge, that is engineered to improve antitumor activity through an immune cloaking strategy with a B2M KO and insertion of a B2M–HLA-E fusion protein to blunt immune-mediated rejection.
◦Preclinical data for CB-011 were presented in a poster at the 2023 Tandem Meeting: Transplantation & Cellular Therapy Meetings of ASTCT and CIBMTR, February 15-19, 2023, in Orlando, Florida. The poster presentation is available on Caribou’s website under Scientific Publications (www.cariboubio.com/technology/#pubs).
◦Additional information on the CaMMouflage trial (NCT05722418) can be found at clinicaltrials.gov (View Source).
•CB-012: Caribou has initiated IND-enabling studies for CB-012, an allogeneic anti-CLL-1 CAR-T cell therapy, to support a planned IND application submission for relapsed or refractory acute myeloid leukemia (r/r AML).
◦CB-012 is the first allogeneic CAR-T cell therapy, to Caribou’s knowledge, with both checkpoint disruption, through a PD-1 KO, and immune cloaking, through a B2M KO and B2M–HLA-E fusion protein insertion; both armoring strategies are designed to improve antitumor activity. CB-012 is engineered with 5 genome edits, enabled by Caribou’s next-generation CRISPR technology platform, which uses Cas12a chRDNA genome editing to significantly improve the specificity of genome edits.
◦In preclinical AML models, CB-012 significantly reduced tumor burden and increased overall survival compared to controls.
•CB-020: Caribou’s first induced pluripotent stem cell (iPSC)-derived allogeneic CAR-NK cell therapy, CB-020, is designed to target solid tumors expressing the tumor antigen ROR1.
◦Preclinical data supporting the selection of the ROR1 CAR construct and armoring strategies for the company’s CAR-NK cell platform were presented at the 12th American Association for Cancer Research (AACR) (Free AACR Whitepaper) and Japanese Cancer Association (AACR-JCA) Joint Conference in December 2022. The poster presentation is available on Caribou’s website under Scientific Publications (www.cariboubio.com/technology/#pubs).

Anticipated 2023 Milestones

•CB-010: Caribou plans to provide an update from the ongoing ANTLER Phase 1 trial for CB-010 in H2 2023.

•CB-011: Caribou recently activated clinical sites for the recruitment of patients at dose level 1 and plans to provide an update on the clearance of dose levels as appropriate from the CaMMouflage Phase 1 trial for CB-011.
•CB-012: Caribou plans to submit an IND application for CB-012 in H2 2023.

Upcoming Investor Conferences

•Caribou management plans to participate in the following investor conferences:
◦March 15: Oppenheimer’s 33rd Annual Healthcare Investor Conference, virtual
◦May 9-11: BofA Securities 2023 Healthcare Conference, Las Vegas

Fourth Quarter and Full Year 2022 Financial Results

Cash, cash equivalents, and marketable securities: Caribou had $317.0 million in cash, cash equivalents, and marketable securities as of December 31, 2022, compared to $413.5 million as of December 31, 2021. Caribou expects these cash, cash equivalents, and marketable securities will be sufficient to fund its current operating plan into 2025.

Licensing and collaboration revenue: Revenue from Caribou’s licensing and collaboration agreements was $3.7 million for the three months ended December 31, 2022 and $13.9 million for the full year 2022, compared to $2.6 and $9.6 million, respectively, for the same periods 2021. The increases were primarily due to revenue recognized under the AbbVie Agreement.
R&D expenses: Research and development expenses were $25.7 million for the three months ended December 31, 2022 and $82.2 million for full year 2022, compared to $15.1 and $52.3 million respectively, for the same periods in 2021. The increases were primarily due to costs to advance pipeline programs; increased headcount, including stock-based compensation; facilities and other allocated expenses; and increased external manufacturing and clinical activities.

G&A expenses: General and administrative expenses were $8.5 million for the three months ended December 31, 2022 and $38.0 million for the full year 2022, compared to $7.9 and $24.3 million, respectively, for the same periods in 2021. The increases were primarily due to increased headcount, including stock-based compensation; legal, accounting, insurance, and other expenses necessary to support the growth and operation of a clinical-stage public company; and facilities and other allocated expenses.
Net loss: Caribou reported a net loss of $27.0 million for the three months ended December 31, 2022 and $99.4 million for the full year 2022, compared to a net loss of $18.5 and $66.9 million, respectively, for the same periods in 2021.

About Caribou’s Novel Next-Generation CRISPR Platform
CRISPR genome editing uses easily designed, modular biological tools to make DNA changes in living cells. There are two basic components of Class 2 CRISPR systems: the nuclease protein that cuts DNA and the RNA molecule(s) that guide the nuclease to generate a site-specific, double-stranded break, leading to an edit at the targeted genomic site. CRISPR systems are capable of editing unintended genomic sites, known as off-target editing, which may lead to harmful effects on cellular function and

phenotype. In response to this challenge, Caribou has developed CRISPR hybrid RNA-DNA guides (chRDNAs; pronounced "chardonnays") that direct substantially more precise genome editing compared to all-RNA guides. Caribou is deploying the power of its Cas12a chRDNA technology to carry out high efficiency multiple edits, including multiplex gene insertions, to develop CRISPR-edited therapies.

On March 9, 2023 Amgen (NASDAQ:AMGN) reported at the 2023 Oppenheimer Healthcare Conference at 2:00 p.m. ET on Monday, March 13, 2023 (Press release, Amgen, MAR 9, 2023, View Source [SID1234628436]). Susan Sweeney, senior vice president, Global Marketing, Access and Capabilities at Amgen will present at the conference. The webcast will be broadcast over the internet simultaneously and will be available to members of the news media, investors and the general public.

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The webcast, as with other selected presentations regarding developments in Amgen’s business given by management at certain investor and medical conferences, can be found on Amgen’s website, www.amgen.com, under Investors. Information regarding presentation times, webcast availability and webcast links are noted on Amgen’s Investor Relations Events Calendar. The webcast will be archived and available for replay for at least 90 days after the event.

On March 9, 2023 VBL Therapeutics (Nasdaq: VBLT) reported today that it has closed on the previously reported sale of its manufacturing facility in Modi’in, Israel, and certain related assets, for $7.1 million in cash to Aleph Farms, an Israel-based food technology company (Press release, VBL Therapeutics, MAR 9, 2023, View Source [SID1234628428]). VBL intends to include the proceeds in the Agreement and Plan of Merger entered into with Notable Labs Inc., announced on February 23, 2023.

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"We are pleased to announce the closing of the sale of our facility, consistent with our plans to unlock value from our assets and maximize shareholder value," said Dror Harats, M.D., Chief Executive Officer of VBL.