On January 10, 2022 BioNTech SE (Nasdaq: BNTX, "BioNTech") and Crescendo Biologics Ltd ("Crescendo"), a clinical stage immuno-oncology company developing novel, targeted T cell enhancing therapeutics, reported that they have entered a multi-target discovery collaboration to develop novel immunotherapies for the treatment of patients with cancer and other diseases. The initial term of the discovery collaboration is three years (Press release, BioNTech, JAN 10, 2022, View Source [SID1234598453]).

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Crescendo will contribute its unique, proprietary, transgenic platform to deliver fully human heavy-chain antibody domains (Humabody VH) against targets nominated by BioNTech. Humabodies represent a novel class of therapeutics that retain the high-affinity binding and specificity of conventional therapeutic antibodies while providing additional advantages such as small size, enhanced tissue and tumor penetration, stability and molecular simplicity due to the lack of a light chain. In particular, the modular nature of Humabodies make them ideally suited for the development of multi-target immunotherapies.

"Crescendo’s platform provides excellent properties for exploiting novel targets and target combinations which we believe has great potential for the development of multi-specific mRNA and engineered cell-based therapies in a variety of disease areas," said Ugur Sahin, M.D., Chief Executive Officer and Co-Founder of BioNTech. "We are excited to begin working with Crescendo to further strengthen and expand our multimodal immunotherapy portfolio and deliver breakthrough precision medicines for patients."

"To collaborate with BioNTech and their world-class team is a transformational opportunity for Crescendo. We are looking forward to further leveraging our clinically validated Humabody VH platform within mRNA therapeutics to develop better treatment options for patients," said Theodora Harold, Chief Executive Officer at Crescendo Biologics.

Under the terms of the agreement, Crescendo will receive $40 million upfront, including a cash payment and an equity investment from BioNTech, as well as research funding for the period of the collaboration. BioNTech will be responsible for global development and hold exclusive worldwide commercialization rights on any products arising from the collaboration. Crescendo will be eligible to receive development, regulatory and commercial milestones up to a total of more than $750 million, in addition to tiered royalties on global net sales.

On January 7, 2022, Century Therapeutics, Inc. (the "Company") reported that entered into a Research, Collaboration and License Agreement (the "Collaboration Agreement") with Bristol-Myers Squibb Company ("BMS") to collaborate on the research, development and commercialization of induced pluripotent stem cell derived, engineered natural killer cell and/or T cell programs for hematologic malignancies and solid tumors (each a "Collaboration Program," and each product candidate developed within such Collaboration Program, a "Development Candidate") (Filing, 8-K, Century Therapeutics, JAN 10, 2022, View Source [SID1234598452]).

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Pursuant to the Collaboration Agreement, the Company and BMS will initially collaborate on two Collaboration Programs and BMS has the option to add up to two additional Collaboration Programs, for an additional fee. The initial two Collaboration Programs are focused on acute myeloid leukemia ("AML") and multiple myeloma, respectively. The two additional Collaboration Programs that BMS may elect to add to the collaboration will focus on targets chosen from a set of reserved targets or other targets selected by BMS, which can be nominated subject to certain conditions agreed with the Company and outlined in the Collaboration Agreement.

Under the Collaboration Agreement, the Company will be responsible for generating Development Candidates for each Collaboration Program with a goal of producing Development Candidates that meet pre-specified criteria. BMS has the option, exercisable for a specified period of time after the Development Candidate for each Collaboration Program is deemed to meet the applicable criteria, to elect to exclusively license from the Company the Development Candidates created in each Collaboration Program for pre-clinical development, clinical development and commercialization on a worldwide basis (each a "License Option"). Following BMS’s exercise of the License Option with respect to a Collaboration Program, the Company will be responsible for performing investigational new drug application ("IND")-enabling studies, supporting BMS’s preparation and submission of an IND and manufacturing of clinical supplies until completion of a proof of concept clinical trial for the relevant Development Candidates, in each case at pre-agreed rates. BMS will be responsible for all regulatory, clinical, manufacturing (after the proof of concept clinical trial) and commercialization activities for such Development Candidates worldwide. The Company has the option to co-promote with BMS Development Candidates generated from the initial AML Collaboration Program and, if BMS elects to expand to a fourth Collaboration Program, Development Candidates generated from the fourth Collaboration Program.

Under the terms of the Collaboration Agreement, BMS will make a non-refundable, upfront cash payment of $100 million to the Company within thirty (30) days of execution of the Collaboration Agreement and will pay the Company an exercise fee upon the exercise of the License Option with respect to a Collaboration Program (each such Collaboration Program, a "Licensed Program" and product candidates developed under a Licensed Program, "Licensed Products"). With respect to each Licensed Program, BMS will pay the Company up to $235 million in milestone payments upon the first achievement of certain development and regulatory milestones within such Licensed Program. In addition, BMS will pay the Company up to $500 million per Licensed Product in net sales-based milestone payments. BMS will also pay the Company tiered royalties per Licensed Product as a percentage of net sales in the high-single digits to low-teens, subject to reduction for biosimilar competition, compulsory licensing and certain third party licenses costs. If Century exercises its co-promote option, such royalty percentage will be increased to low-teens to high-teens in respect of the sales of the co-promoted Licensed Products in the United States. The royalty term shall terminate on a Licensed Product-by-Licensed Product and country-by-country basis on the latest of (i) the twelve (12) year anniversary of the first commercial sale of such Licensed Product in such country, (ii) the expiration of any regulatory exclusivity period that covers such Licensed Product in such country, and (iii) the expiration of the last-to-expire licensed patent of the Company or a jointly owned patent that covers such the Licensed Product in such country. After expiration of the applicable royalty term for a Licensed Product in a country, all licenses granted by the Company to BMS for such Licensed Product in such country will be fully paid-up, royalty-free, perpetual and irrevocable.

The Collaboration Agreement includes customary representations and warranties, covenants and indemnification obligations for a transaction of this nature. The Company and BMS each have the right to terminate the agreement for material breach by, or insolvency of, the other party following notice, and if applicable, a cure period. BMS may also terminate the Collaboration Agreement in its entirety, or on a program-by-program basis, for convenience upon ninety (90) days’ notice.

The foregoing description of the Collaboration Agreement does not purport to be complete and is qualified in its entirety by reference to the text of the Collaboration Agreement. A copy of the Collaboration Agreement will be filed as an exhibit to the Company’s Quarterly Report on Form 10-Q for the quarter ending March 31, 2022.

Securities Purchase Agreement

In connection with the Collaboration Agreement, the Company and BMS entered into a Securities Purchase Agreement (the "Purchase Agreement") on January 7, 2022, whereby the Company issued and sold and BMS purchased 2,160,760 shares of the Company’s common stock, par value $0.0001 per share (the "Common Stock") (the "Shares") at a price per share of $23.14, for an aggregate purchase price of $50 million. The Company and BMS expect to close on the purchase and sale of the Shares on January 12, 2022.

On January 10, 2022 Bristol Myers Squibb (NYSE:BMY) reported that it will highlight progress against the Company’s growth strategy and outlook for 2022 during a presentation scheduled at 7:30 a.m. ET at the 40th Annual J.P. Morgan Healthcare Conference (Press release, Bristol-Myers Squibb, JAN 10, 2022, View Source [SID1234598451]).

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"We are successfully transforming the company by further diversifying our product portfolio, launching breakthrough new medicines that benefit our patients and advancing a robust product pipeline that will help us deliver sustained growth," said Giovanni Caforio, M.D., board chair and chief executive officer, Bristol Myers Squibb. "We are entering 2022 excited about the growth opportunities in our in-line brands and new product portfolio. With our strong financial position, we continue to invest in internal and external innovation to further enhance and diversify our pipeline, while delivering new medicines to patients with serious disease and creating long-term value for our shareholders."

Highlights of the presentation

Bristol Myers Squibb’s presentation will focus on four key drivers positioning the Company for sustained growth and value creation, helping to offset losses of exclusivity in the coming years. The drivers build upon a strong foundation of existing in-line products, including Opdivo(nivolumab), Yervoy(ipilimumab)and Eliquis(apixaban), which are expected to contribute approximately $8-$10 billion in revenue growth during the period of 2020-2025. The drivers include:

New product portfolio with significant growth potential. With six recent launches (Abecma(idecabtagene vicleucel),Breyanzi (lisocabtagene maraleucel), Inrebic(fedratinib), Onureg(azacytidine), Reblozyl (luspatercept-aamt)andZeposia(ozanimod)) and three launches anticipated in 2022 (relatimab and nivolumab fixed dose combination,mavacamten, deucravacitinib), Bristol Myers Squibb’s renewed and diverse product portfolio has the potential to deliver:
$10-$13 billion of risk-adjusted revenue in 2025;
More than $25 billion non-risk-adjusted revenue in 2029; and
At least $4 billion of non-risk adjusted revenue in 2029 for each of the following recent or anticipated new products: Reblozyl,relatimab and nivolumab fixed dose combination,mavacamten and deucravacitinib.
Promising mid- to late-stage assets with large commercial opportunities. Bristol Myers Squibb has seven key assets in its mid-to-late-stage pipeline focused on disease areas where there are meaningful opportunities to improve outcomes for patients. These assets include milvexian, which has demonstrated a differentiated profile as a next generation anti-thrombotic therapy, and two novel CELMoDs, iberdomide and CC-92480, with potential to be new foundational treatments in multiple myeloma.
Powerful innovation engine driving a broad early-stage pipeline. With more than 50 assets in its early-stage pipeline and the opportunity for more than 20 proof of concept decisions over the next three years, Bristol Myers Squibb is advancing one of the most exciting pipelines in the industry, amplified by the Company’s strong external partnerships.
Strong cash flow generation provides significant financial strength and flexibility. Bristol Myers Squibb plans to leverage its $45-$50 billion in expected free cash flow between 2022 and 2024 to execute a consistent, balanced capital allocation strategy, prioritizing business development and returning cash to shareholders through the Company’s dividend and share repurchase program. The Company remains committed to maintaining a strong investment grade rating and reducing debt.
Announcement of Accelerated Share Repurchase Program

Today, the Company also announced that it plans to execute an accelerated share repurchase (ASR) agreement during the first quarter of 2022 to repurchase up to $5 billion of Bristol Myers Squibb common stock. The ASR is part of the Company’s previously disclosed multi-year $15 billion share repurchase authorization.

The total number of shares ultimately repurchased will be determined upon final settlement and will be based on a discount to the volume-weighted average price of Bristol Myers Squibb’s common stock during the ASR period.

Introduction of 2022 Financial Guidance

Bristol Myers Squibb is introducing the following guidance metrics for 2022:

Total company revenues are expected to be approximately $47 billion, representing an increase in the low-single digits.
Sales from key loss of exclusivity (LOE) brands, which represent Revlimid and Abraxane (paclitaxel protein-bound particles for injectable suspension) (albumin-bound), are expected to be approximately $10.5 billion. Revlimid sales are expected to be $9.5-$10 billion.
Our Continuing Business is expected to grow in the low-double digits and contribute approximately $36.5 billion in 2022 with growth from the new product portfolio and in-line products.
The Company’s non-GAAP EPS guidance is expected to be in the range of $7.65 – $7.95. Non-GAAP EPS guidance assumes current exchange rates.
The Company intends to provide additional 2022 financial guidance during its 2021 fourth quarter earnings conference call on February 4, 2022.

The 2022 financial guidance excludes the impact of any potential future strategic acquisitions and divestitures, and any specified items that have not yet been identified and quantified. The 2022 non-GAAP EPS guidance is further explained under "Use of Non-GAAP Financial Information." The financial guidance is subject to risks and uncertainties applicable to all forward-looking statements as described elsewhere in this press release.

Reaffirms Long-Term Financial Targets

Bristol Myers Squibb is also reaffirming its 2020-2025 long-term revenue and operating margin targets communicated in January 2021. The Company is extending its previously communicated guidance for free cash flow for an additional year as detailed below:

Expects low to mid-single digit revenue CAGR and low double-digit revenue CAGR excluding Revlimid and Pomalyst (pomalidomide)at constant exchange rates
Expects to maintain low to mid-40s percent non-GAAP operating margin
Expects significant cash flow generation of $45-$50 billion dollars from 2022-2024 compared to prior guidance of $45-$50 billion dollars from 2021-2023
This financial guidance excludes the impact of any potential future strategic acquisitions and divestitures as well as any specified items as discussed under "Use of Non-GAAP Financial Information." There is no reliable or reasonably estimable comparable GAAP measures for this non-GAAP financial guidance. The financial guidance is subject to risks and uncertainties applicable to all forward-looking statements as described elsewhere in this press release.

Company and Webcast Information

Bristol Myers Squibb is a global biopharmaceutical company whose mission is to discover, develop and deliver innovative medicines that help patients prevail over serious diseases. For more information about Bristol Myers Squibb, visit us at BMS.com or follow us on LinkedIn, Twitter, YouTube, Facebook, and Instagram.

Investors and the general public are invited to listen to a live webcast of the J.P. Morgan presentation at View Source Materials related to the presentation will be available at the same website at the start of the live webcast. An archived edition of the presentation will be available later that day.

Corporate-Financial News

Use of Non-GAAP Financial Information

In discussing financial results and guidance, the company refers to financial measures that are not in accordance with U.S. Generally Accepted Accounting Principles (GAAP), including non-GAAP EPS, operating margin and free cash flow. These non-GAAP financial measures may provide investors with additional useful information. For example, non-GAAP earnings and EPS information are indications of the company’s baseline performance before items that are considered by us to not be reflective of the company’s ongoing results. This information is among the primary indicators that we use as a basis for evaluating performance, allocating resources, setting incentive compensation targets and planning and forecasting for future periods. In addition, non-GAAP operating margin, which is operating income excluding certain specified items as a percentage of revenues, is relevant and useful for investors because it allows investors to view performance in a manner similar to the method used by our management and make it easier for investors, analysts and peers to compare our operating performance to other companies in our industry and to compare our year-over-year results.

Because the non-GAAP financial measures are not calculated in accordance with GAAP, they should not be considered superior to and are not intended to be considered in isolation or as a substitute for the related GAAP financial measures and may not be the same as or comparable to similarly titled measures presented by other companies due to possible differences in method and in the items being adjusted. We encourage investors to review our financial statements and publicly-filed reports in their entirety and not to rely on any single financial measure.

Also note that a reconciliation of the forward-looking non-GAAP EPS, free cash flow, and operating margin measures is not provided due to no reasonably accessible or reliable comparable GAAP measures and the inherent difficulty in forecasting and quantifying such measures that are necessary for such reconciliation. Namely, we are not able to reliably predict the impact of specified items or currency exchange rates beyond the next twelve months. As a result, the reconciliation of these non-GAAP measures to the most directly comparable GAAP measures is not available without unreasonable effort. In addition, the company believes such a reconciliation would imply a degree of precision and certainty that could be confusing to investors. The variability of the specified items may have a significant and unpredictable impact on our future GAAP results.

Website Information

We routinely post important information for investors on our website, BMS.com, in the "Investors" section. We may use this website as a means of disclosing material, non-public information and for complying with our disclosure obligations under Regulation FD. Accordingly, investors should monitor the Investors section of our website, in addition to following our press releases, SEC filings, public conference calls, presentations and webcasts. We may also use social media channels to communicate with our investors and the public about our company, our products and other matters, and those communications could be deemed to be material information. The information contained on, or that may be accessed through, our website or social media channels are not incorporated by reference into, and are not a part of, this document.

On January 10, 2022 LUMICKS, a next generation life science tools provider, reported that two major centers of excellence in cancer immunology have adopted LUMICKS’ z-Movi Cell Avidity Analyzer instrument (Press release, LUMICKS, JAN 10, 2022, View Source;utm_medium=rss&utm_campaign=z-movi-cell-avidity-analyzer-fred-hutch-oxford-university [SID1234598450]).

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The first placement is at Fred Hutchinson Cancer Research Center ("Fred Hutch") in Seattle, Washington, USA, a leading research institute dedicated to the eradication of cancer. The instrument is housed at the Immune Monitoring Core Facility and serves multiple immuno-oncology and cell therapy research groups from the Center to accelerate immunotherapy development for cancer treatments.

The second z-Movi is placed at the University of Oxford, in Oxford, UK, in the lab of Prof. Tim Elliott, a world leader in the field of antigen presentation and T cell biology. The teams of Prof. Elliott and Prof. Persephone Borrow are using the instrument to investigate a broad range of T cell–target interactions including the potency and longevity of T cells in solid tumors.

"The z-Movi Cell Avidity Analyzer provides an excellent platform for quantitating the avidity of interactions occurring between T cells and cognate antigen-presenting target cells during the induction and effector phases of an immune response." said Prof. Elliott and Prof. Borrow. "This enables dissection of attributes of both T cells and their interaction partners that influence the response to viral infections and cancer."

"We are delighted that our z-Movi instrument will be adopted into the workflows at Fred Hutch and University of Oxford, two institutions devoted to the development of promising immunotherapeutic strategies," said LUMICKS CSO Dr. Andrea Candelli. "At LUMICKS, we are focused on developing new technologies that help cancer researchers discover new therapies. We believe that cell avidity measurements provide unique insights into the mechanism of action of cell therapy products, ultimately leading to higher success rates for novel cancer immunotherapies."

On January 10, 2022 HUTCHMED (China) Limited ("HUTCHMED") (Nasdaq/AIM:HCM; HKEX:13) reported that it has initiated a Phase I study in China of HMPL-760, a highly potent, selective, and reversible inhibitor with long target engagement against Bruton’s tyrosine kinase ("BTK"), including wild-type and C481S-mutated BTK. The first patient received their first dose on January 4, 2022.

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The clinical study is a multi-center, open-label study to evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD) and preliminary efficacy profile of HMPL-760. The study is enrolling patients with previously treated chronic lymphocytic leukemia/​small lymphocytic lymphoma (CLL/SLL) or other types of Non-Hodgkin Lymphoma ("NHL"), including patients treated with a prior regimen containing a BTK inhibitor, whose disease carries either wild-type BTK or acquired resistance to first generation BTK inhibitors due to additional mutations to BTK.

An initial dose escalation stage to determine the maximum tolerated dose (MTD) and/or the recommended Phase II dose ("RP2D") is planned, to be followed by a dose expansion phase where patients will receive HMPL‑760 to further evaluate the safety, tolerability, and clinical activity at the RP2D. Approximately 100 patients are expected to be enrolled.

HMPL-760 is HUTCHMED’s fifth investigational drug candidate targeting hematological malignancies in clinical development. Amdizalisib (HMPL-689, targeting the delta isoform of phosphoinositide 3-kinase or PI3K delta) and HMPL-523 (targeting spleen tyrosine kinase or Syk) are also being studied in several Phase II trials against B-cell dominant malignancies. Phase II registration studies are underway in China for amdizalisib in patients with follicular lymphoma (FL), for which it has been granted Breakthrough Therapy Designation in China, and marginal zone lymphoma (MZL).

In addition to the three BCR inhibitors, for hematological malignancies HUTCHMED is also developing its in-house discovered drug candidate HMPL-306, a dual-inhibitor of mutant isocitrate dehydrogenase 1 and 2, and tazemetostat, a methyl­transferase inhibitor of EZH2 (being developed in Greater China by HUTCHMED pursuant to a strategic collaboration with Epizyme).

About BTK and Non-Hodgkin Lymphoma
BTK is a key component of the B-cell receptor signaling pathway and is an important regulator of cell prolifera­tion and cell survival in various lymphomas. The abnormal activation of B-cell receptor signaling is closely related to the development of B-cell type hemato­logical cancers, which represent approximately 85% of all NHL cases.[1] BTK is considered a validated target for drugs that aim to treat certain hemato­logical cancers, however C481S mutation of BTK is a known resistance mechanism for first and second generation BTK inhibitors. In 2020, approximately 93,000 new cases of NHL are estimated to have been diagnosed in China.[2]

About HMPL-760
HMPL-760 is an investigational, highly selective, non-covalent, third-generation inhibitor of BTK, both wild-type and C481S mutant enzymes, with pre-clinical data suggesting high target specificity and higher potency versus first generation BTK inhibitors. BTK C481S mutation plays an important role in resistance to certain BTK inhibitors.[3],[4]

HMPL-760 is HUTCHMED’s eleventh innovative potential oncology drug candidate to enter clinical develop­ment. HUTCHMED currently retains all rights to HMPL-760 worldwide.