On March 9, 2023 Ad hoc announcement pursuant to Art. 53 LR: Molecular Partners AG (SIX: MOLN, NASDAQ: MOLN), a clinical-stage biotech company developing a new class of custom-built proteins known as DARPin therapeutics, reported its corporate highlights and audited financial results for the full year 2022 (Press release, Molecular Partners, MAR 9, 2023, View Source [SID1234628441]).

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"Our focus in 2023 is the advancement of highly differentiated DARPin therapeutic candidates with the potential to show early clinical value. Recently we dosed the first patient with MP0533, our novel tri-specific T-cell engager for the treatment of AML and high risk MDS. We also announced a breakthrough with our Radio DARPin Therapy Platform which enables us to reduce dose-limiting kidney uptake and potentially opens the door for a pipeline of new candidates, of which the first is targeting Delta-like ligand 3 (DLL3). MP0317, our localized CD40 agonist, has reached its top planned dose without limiting side effects, showing a clear differential against conventional systemically active agonists," said Patrick Amstutz, Ph.D. Molecular Partners’ Chief Executive Officer. "With our ongoing strong cash position, we will continue to advance our DARPin candidates to deliver on our mission to develop solutions only DARPin therapies can offer to patients living with serious diseases."

Research & Development Highlights

Oncology

MP0317
In November 2022, Molecular Partners presented interim results from the ongoing Phase 1 trial of MP0317, the Company’s DARPin candidate targeting fibroblast activation protein (FAP) and CD40, for the treatment of solid tumors at the 37th SITC (Free SITC Whitepaper) Annual meeting. These data demonstrated the first clinical observation of tumor-localized CD40 activation provided by MP0317. The candidate was also seen to be safe and well tolerated with no dose-limiting CD40-related systemic toxicities to date, a key limitation presented by other CD40 agonists. MP0317 is designed to resolve these limitations by activating immune cells specifically within the tumor microenvironment through the simultaneous binding of the immune stimulator CD40 as well as FAP, a protein highly expressed within tumors. The dose escalation of the Phase 1 study remains ongoing, with patient recruitment in the dose escalation portion of the of the Phase 1 trial of MP0317 expected to be completed in the first half of 2023.

MP0533
In January 2023, the first patient was dosed in Molecular Partners’ Phase 1 study of MP0533, a novel tri-specific T-cell engager for the treatment of AML and high risk MDS. The first clinical results from this trial are expected by the fourth quarter of 2023. In an oral presentation at the 64th Annual ASH (Free ASH Whitepaper) Meeting in December 2022, Molecular Partners presented preclinical results showing MP0533 can induce preferential killing of cells expressing two or three tumor-associated antigens (TAAs) compared to cells expressing a single TAA. MP0533 engages CD3 on T-cells while binding up to three tumor-associated antigens (CD33, CD70, and CD123) on AML cells. By modulating the affinity to each TAA, Molecular Partners designed MP0533 to induce T-cell-mediated killing preferentially when the cancer cells express two or three of the TAAs. This avidity-driven T-cell activation ensures preferential killing of AML cells, which consistently express two or three of the target antigens. At the same time, it is designed to reduce the damage to healthy cells, which tend to express only one of the target antigens, a recurrent issue with other T-cell engagers in AML. MP0533 was demonstrated to activate T-cells and destroy AML cells in samples from newly diagnosed and previously treated AML patients with different TAA expressions. Humanized mouse models confirmed MP0533’s ability to activate intra-tumoral T-cells and control tumor growth. The research also showed that MP0533 was able to directly target and kill leukemic stem cells (LSCs), while sparing a variety of healthy cells including hematopoietic stem cells. The unique safety profile of MP0533 was further supported preclinically by several other parameters including a lower level of cytokine release relative to benchmark mono-targeted T-cell engagers, both in vitro in a whole blood assay and in vivo in the humanized mouse AML models.

Radio DARPin Therapy Platform
In 2022, Molecular Partners progressed its Radio DARPin Therapy Platform by reducing the kidney uptake of DARPin radio conjugates to overcome nephrotoxicity (toxicity in the kidney), the key limitation of protein-based radio therapies. Furthermore, tumor-associated protein Delta-like ligand 3 (DLL3) was selected as the first target of a DARPin-based therapeutic candidate. Expression of DLL3 is low in healthy tissue but significantly increased in certain tumor types, providing an opportunity for selective targeting through the high affinity and specificity offered by DARPins. These attributes, along with their small size, suggest that DARPins represent ideal delivery vectors for therapeutic radionuclides to efficiently target cancer cells with minimal systemic side effects. Molecular Partners is developing DARPin-based therapeutic candidates, both proprietary as well as in collaboration with Novartis. The Company plans to present its research of DARPin therapeutic candidates and their potential differentiation as tumor targeting moieties in the first half of 2023.

Virology

An Emergency Use Authorization (EUA) application was submitted to the U.S. Food and Drug Administration on February 4, 2022 following the successful global EMPATHY clinical study which demonstrated the efficacy and safety of ensovibep, the first DARPin-based antiviral molecule. Ensovibep also demonstrated in vitro efficacy against most Variants of Concern relative to some antibody therapies, a characteristic Molecular Partners intends to continue leveraging in further antiviral candidates. The clinical development of ensovibep was halted in 2022 due to a lack of neutralization activity against omicron subvariants.

Earlier this year, Novartis informed Molecular Partners that it had submitted a request to withdraw ensovibep’s EUA from the FDA. The EUA application for ensovibep was withdrawn effective January 25, 2023.

Looking ahead for the virology portfolio, in January 2023 Molecular Partners signed a non-binding letter of intent with Novartis to negotiate a Research Framework Agreement with a primary focus on establishing pandemic preparedness and fighting emerging infectious global health threats.

Ophthalmology

In November 2021, Molecular Partners regained global development and commercial rights to abicipar for the treatment of neovascular age-related macular degeneration (nAMD) and Diabetic Macular Edema (DME). Abicipar completed two positive Phase 3 studies, CEDAR and SEQUOIA, which supported the non-inferior efficacy of its quarterly dosing regimen compared to monthly ranibizumab.

The Company continues to evaluate potential business opportunities for abicipar outside of internal development at Molecular Partners.

Corporate Governance and Leadership Highlights

Chief Executive Officer Patrick Amstutz was elected as President of the Swiss Biotech Association Board of Directors effective May 3, 2022. Switzerland has become one of the global hubs for life sciences and this position will allow Patrick the opportunity to provide leadership and influence in the biopharma industry both regionally and globally.

Alexander Zürcher was promoted to Chief Operating Officer, effective July 1, 2022. Coinciding with Alexander’s promotion, Michael Stumpp, the Company’s prior COO, transitioned to the newly formed position of EVP Projects while remaining a member of the Company’s Management Board. Renate Gloggner was promoted to EVP People and Community, effective as of July 1, 2022. Both Alexander and Renate were appointed to the Company’s Management Board, also effective as of July 1, 2022.

Michael Pitzner appointed General Counsel and Senior Vice President of Legal effective November 1, 2022. Most recently Michael served as Head Legal Biologics, Cell & Gene and CMO (Global NTO) at Novartis.

Anne Goubier, D.V.M, Ph.D., was promoted to Senior Vice President of Biology. Anne joined Molecular Partners in 2020 and oversees the biology department, overseeing development from target identification to clinical pharmacology, building on her more than two decades of biotechnology experience across drug discovery and development.

CFO Andreas Emmenegger departed the company as of Dec. 31, 2022 following a successful tenure of more than 15 years. His successor will be announced in due course and we are committed to a smooth transition.

ESG initiatives

In 2022, Molecular Partners published its environmental, social and governance (ESG) priorities and progress, accessible on the investors section of its website. Currently, the Company is creating a baseline status evaluation as the next step toward implementing an ESG plan with clear metrics that detail its progress across priority areas: board oversight of ESG and corporate sustainability; human capital management and Diversity, Equity and Inclusion (DEI); product service and safety; access to medicine; and business ethics.

In its continued commitment to corporate sustainability, Molecular Partners advanced its ESG goal by formally establishing corporate sustainability responsibility at a Board level. The Finance and Audit Committee will lead oversight of all ESG policies for the Board. To fully integrate the Company’s ESG strategy within the organization, Molecular Partners has created an ESG Circle of key internal stakeholders to ensure continued progress is made across key priorities. Elsewhere, Molecular Partners offers generous benefits spanning from health to retirement planning to its employees, and fosters diversity and inclusion as a key element of its recruitment process.

2022 Operational and Financial Highlights

Following Novartis’ payment of CHF 150 million for ensovibep in January 2022, Molecular Partners remains well funded to capture upcoming value inflection points in 2023 and beyond. In the financial year 2022, Molecular Partners recognized total revenues and other income of CHF 189.6 million (2021: CHF 9.8 million) and incurred total expenses of CHF 73.0 million (2021: CHF 73.2 million). This led to an operating profit of CHF 116.6 million for 2022 (2021: Operating loss of CHF 63.4 million). The net financial gain recorded in 2022 was CHF 1.2 million, compared to a net financial loss of CHF 0.4 million in 2021. This resulted in a 2022 net profit of CHF 117.8 million (2021: Net loss of CHF 63.8 million).

The net cash from operating activities in 2022 was CHF 118.6 million (2021: Net cash used of CHF 91.0 million). Including short-term time deposits, the cash and cash equivalents position increased by CHF 116.3 million as compared to year-end 2021, to CHF 249.1 million as of December 31, 2022 (December 31, 2021: CHF 132.8 million). Total shareholders’ equity stood at CHF 235.2 million as of December 31, 2022, an increase of CHF 127.9 million (December 31, 2021: CHF 107.3 million).

The Company’s cash position and short-term time deposits of total CHF 249.1 million as per December 31, 2022, continues to provide the Company with financial flexibility and a forecasted cash runway into 2026.

The Company’s balance sheet continued to be debt-free in 2022. As of December 31, 2022, the Company employed 175.3 FTE (full-time equivalents), up 7% year-on-year. About 81% of the employees are employed in R&D-related functions.

Key figures as of December 31, 2022

Key Financials (CHF million, except per share, FTE data) FY 2022 FY 2021 Change
Total revenues and other income 189.6 9.8 179.8
R&D expenses (50.7 ) (55.7 ) 5.0
SG&A expenses (22.3 ) (17.5 ) (4.8 )
Operating result 116.6 (63.4 ) 180.0
Net finance result 1.2 (0.4 ) 1.6
Net result 117.8 (63.8 ) 181.6
Basic net result per share (in CHF) 3.63 (2.06 ) 5.69
Diluted net result per share (in CHF) 3.54 (2.06 ) 5.60
Net cash from (used in) operating activities 118.6 (91.0 ) 209.5
Cash & cash equivalents (incl. short-term time deposits) 249.1 132.8 116.3
Total shareholders’ equity 235.2 107.3 127.9
Number of total FTE 175.3 163.2 12.1

Business outlook and priorities

In 2023, the Company will continue to invest in its clinical stage assets as well as in its development portfolio, particularly in the areas of Radio DARPin therapeutics, oncology, and virology. With initial data from the phase 1 study of MP0533 expected before the end of the year, the potential to further integrate this program as a later stage, wholly-owned asset remains strong. The conclusion of recruitment in the phase 1 study of MP0317 will provide an opportunity to discuss additional combination work with potential collaborators.

As we continue to detail our work in Radio DARPins with presentations at scientific congresses throughout the year, we aim to demonstrate that DARPins can serve as high-affinity tumor targeting therapeutics while providing a high level of kidney protection, a common limiting toxicity associated with other radio therapies. In addition, we continue to remain excited about the prospect of DARPins in virology, within the potential of our own pipeline and with our newly announced letter of intent with Novartis to explore the potential of DARPins in emerging global health threats.

Financial outlook 2023

For the full year 2023, at constant exchange rates, the Company expects total operating expenses of CHF 70-80 million, of which around CHF 9 million will be non-cash effective costs for share-based payments, IFRS pension accounting and depreciation.

Based on the Company’s cash position as of December 31, 2022, the Company expects its cash runway to reach into 2026, excluding any potential receipts from R&D partners.

Documentation

This press release, the Company’s Annual Report on Form 20-F for the year ended December 31, 2022 to be filed with the U.S. Securities and Exchange Commission (SEC), and the Company’s annual report 2022 will be made available through www.molecularpartners.com under the investor section after 22.00 CET (16.00 EST) on March 9, 2023.

Full year 2022 conference call & audio webcast

Molecular Partners will hold a conference call and audio webcast on March 10, 14.00 CET (8.00 am EST).
To register for the full year 2022 conference call, please dial the following numbers approximately 10 minutes before the start of the presentation:

Switzerland / Europe +41 800 83 6507
USA +1 844 865 3856
Full list of dial-in numbers linked here

Conference ID Please ask to be joined into the Molecular Partners call.

Participants in the conference call will have the opportunity to ask questions after the presentation.

Audio webcast

The full year 2022 results will be webcast live and will be made available on the Company’s website under the investor section. The replay will be available for 90 days following the presentation.

Financial calendar

April 4, 2023 Annual General Meeting
May 11, 2023 Interim Management Statement Q1 2023
August 24, 2023 Half-year results 2023 (unaudited)
October 26, 2023 Interim Management Statement Q3 2023
The latest timing of the above events can always be viewed on the investor section of the website.

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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Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

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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.