On March 22, 2022 2seventy bio, Inc. (Nasdaq: TSVT), a leading immuno-oncology cell therapy company, reported financial results and recent highlights for the fourth quarter and year ended December 31, 2021 (Press release, 2seventy bio, MAR 22, 2022, View Source [SID1234610566]).

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"We launched 2seventy bio at the end of 2021 with incredible starting material. We have a transformative commercial product in ABECMA, a pipeline with multiple clinical stage programs, next-generation technologies that will enable us to continue to be at the forefront of cell therapy innovation, and a passionate team that is committed to the cause," said Nick Leschly, chief kairos officer. "We’ve had a strong start to 2022. We have reshaped our operating model and taken important steps to reduce our overhead costs. We are taking a disciplined approach to our budgets to ensure that we optimize our R&D investment and drive towards value-creating milestones. Together with our partner Bristol Myers Squibb, we have made important progress on unlocking additional ABECMA manufacturing capacity and expect additional increases to capacity in the second half of the year as we continue to deliver for multiple myeloma patients in need of treatment options. And, we have secured additional capital during challenging market conditions from leading life sciences investors in the business. Taken together, we expect that we will have a sufficient financial foundation to execute on our patient mission into 2025. We are fired up and look forward to great things this year and beyond!"

PIPE FINANCING

On March 17, 2022, the company closed a $170 million private placement. The private placement included top healthcare investors, including 683 Capital, Armistice Capital, Bain Capital Life Sciences, Boxer Capital, CaaS Capital, Casdin Capital, Cowen Healthcare Investments, EcoR1 Capital, Heights Capital, Janus Henderson Investors, Madison Avenue Partners, Newtyn Management, Nick Leschly & family, RTW Investments, LP, and existing investors.

COMMERCIAL PROGRESS

Bristol Myers Squibb reported total U.S. ABECMA (idecabtagene vicleucel; ide-cel) fourth quarter revenues of $67 million and full year 2021 U.S. ABECMA revenues of $158 million. 2seventy bio and Bristol Myers Squibb share equally in all profits and losses related to developing, manufacturing and commercializing ABECMA in the U.S. In 2022, 2seventy anticipates total U.S. ABECMA revenues of $250-$300 million and we are tracking to the high end of the range bolstered by a significant patient backlog, continued high demand for a proven treatment and increasing manufacturing capacity.

Given the high unmet medical need and strong patient demand, we believe there is meaningful opportunity for multiple BCMA CAR-T products. Our primary focus for the next one to two years is on increasing our manufacturing capacity in partnership with regulators. The U.S. business will fully utilize the expanding capacity as it becomes available, and we will build on our experience in the commercial setting to deliver ABECMA for multiple myeloma patients in need. We continue to anticipate that ABECMA will be sustainably cash flow positive for 2seventy bio, inclusive of R&D costs, by the end of 2022, and will continue to grow in 2023 and beyond.

UPDATED CASH SPEND GUIDANCE

2seventy bio has taken important steps to reduce overhead costs and streamline our operating model. We expect that these changes, combined with an improved outlook for ABECMA, will enable us to decrease net cash spend for 2022. We are reducing our original net cash spend guidance of $220-250 million down to a lower range of $190-220 million. Together with the proceeds from the recently completed private placement, the company now anticipates that it has sufficient cash to fund current planned operations into 2025. The increased financial runway is expected to bring 2seventy bio through meaningful clinical data updates, new INDs and additional commercial progress.

RECENT HIGHLIGHTS

bbT369 PRECLINICAL DATA AT AACR (Free AACR Whitepaper) – Today, 2seventy bio is announcing that preclinical data from bbT369, an investigational dual-targeted CAR T cell therapy with a CBLB gene edit for patients with relapsed/refractory B cell non-Hodgkin lymphoma (B-NHL), has been accepted for poster presentation at the American Association of Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2022 on Sunday, April 10 in New Orleans, LA. Mike Certo, Ph.D., VP of Genome Editing at 2seventy bio, will present Poster 581, titled "bbT369, a dual-targeted and CBLB gene-edited autologous CART product, demonstrates anti-lymphoma activity in preclinical mouse models," on Sunday, April 10, 1:30-5:30 PM CT. An E-Poster will be available on the AACR (Free AACR Whitepaper) website starting Friday, April 8 at 1:00 PM ET through Wednesday, July 13.
MANAGEMENT APPOINTMENTS – On February 14, 2022, 2seventy bio announced that Steven Bernstein, M.D. joined the company in the role of chief medical officer. Additionally, Susan Abu-Absi, Ph.D. was appointed chief technology & manufacturing officer.
UPCOMING ANTICIPATED MILESTONES

ABECMA

Anticipated $250-300 million total U.S. commercial revenue in 2022, shared with Bristol Myers Squibb
Increasing manufacturing capacity expected over 2022 and 2023
KarMMa-2 study in high-risk multiple myeloma proof-of-concept data in 2022
KarMMa-3 study in 3L+ registrational data in 2023 with potential FDA approval in 2023-2024
Pipeline

Presentation of preclinical data from bbT369 program in B-NHL at AACR (Free AACR Whitepaper) Annual Meeting 2022
Infusion of first patients in CRC-403 study of bbT369 in B-NHL in 2022
Initial assessment of feasibility of bbT369 drug product manufacturing and patient safety in 2H 2022
Infusion of first patients in PLAT-08 study of SC-DARIC33 in AML in 2022
Initial assessment of feasibility of SC-DARIC33 drug product manufacturing and drug regulated anti-CD33 activity in 2H 2022
SELECT FOURTH QUARTER AND FULL YEAR 2021 FINANCIAL RESULTS

Bristol Myers Squibb reported total U.S. revenues of $67 million and $158 million for ABECMA for the three and twelve months ended December 31, 2021, respectively. 2seventy bio and Bristol Myers Squibb share equally in all profits and losses related to development, manufacturing and commercializing ABECMA in the U.S. We reported collaborative arrangement revenue of $11.4 million and $26.9 million for the three and twelve months ended December 31, 2021, respectively, which includes our share of gross profit less costs associated with the commercialization of ABECMA in the U.S.
Total revenues were $16.0 million for the three months ended December 31, 2021, compared to $9.9 million for the three months ended December 31, 2020. Total revenues were $54.5 million for the twelve months ended December 31, 2021 compared to $248.1 million for the twelve months ended December 31, 2020. The increase for the three-month period was primarily driven by collaborative arrangement revenue recognized as a result of sales of ABECMA in the fourth quarter of 2021. The decrease for the twelve-month period was driven by one-time revenue recorded in connection with the May 2020 Bristol Myers Squibb contract modification in the second quarter of 2020.
Research and development expenses were $59.5 million for the three months ended December 31, 2021, compared to $68.9 million for the three months ended December 31, 2020. Research and development expenses were $261.9 million for the twelve months ended December 31, 2021 compared to $296.5 million for the twelve months ended December 31, 2020. The decrease for the three-month period was primarily driven by decreased development costs under our agreement with Bristol Myers Squibb due to a focus on directing manufacturing capacity to commercial ABECMA patients following approval in 2021. The decrease for the twelve-month period was primarily driven by decreased manufacturing expenses as a result of Bristol Myers Squibb’s assumption of the contract manufacturing agreement relating to ide-cel adherent lentiviral vector as part of the May 2020 Bristol Myers Squibb contract modification and an overall decrease in drug product manufacturing for the CRB-402 study, as the study has come to conclusion.
Selling, general and administrative expenses were $24.5 million for the three months ended December 31, 2021, compared to $21.9 million for the three months ended December 31, 2020. Selling, general and administrative expenses were $93.5 million for the twelve months ended December 31, 2021 compared to $90.9 million for the twelve months ended December 31, 2020. The increase for both periods was primarily driven by increased commercial costs to support the commercialization of ABECMA and IT and other facility-related costs in connection with the spin-off from bluebird bio.
Net loss was $61.0 million for the three months ended December 31, 2021, compared to $76.8 million for the year ended December 31, 2020. Net loss was $292.2 million for the twelve months ended December 31, 2021, compared to $120.1 million for the twelve months ended December 31, 2020.
2seventy bio ended 2021 with cash, cash equivalents and marketable securities of $362.2 million.

On March 22, 2022 Mission Therapeutics ("Mission"), a drug discovery and development company focused on protein homeostasis by selectively inhibiting deubiquitylating enzymes (DUBs), reported that Dr Paul Wallace, Chief Business Officer, will attend the sixteenth annual BIO-Europe Spring conference (28-31 March) (Press release, Mission Therapeutics, MAR 22, 2022, View Source [SID1234610561]).

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BIO-Europe Spring is one of the most international gatherings in the biopharma industry, bringing together the life science community for global dealmaking. Dr Paul Wallace will join participants from other leading companies in the sector, attending meetings, panel discussions, and showcases, and is available for one-to-one meetings. The event is being held virtually.

On March 22, 2022 MannKind Corporation (Nasdaq: MNKD), a company focused on the development and commercialization of inhaled therapeutic products for patients with endocrine and orphan lung diseases, reported that its Chief Scientific Officer, Thomas Hofmann, MD, PhD, will participate in the Cantor Virtual Rare Orphan Disease Summit on Tuesday, March 29, 2022 at 8:00 am (PT) (Press release, Mannkind, MAR 22, 2022, View Source [SID1234610560]).

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If you have interest in participating in the Cantor Virtual Rare Orphan Disease Summit, please reach out to your Cantor Fitzgerald representative.

On March 22, 2022 Lantern Pharma Inc. (NASDAQ: LTRN), a clinical stage biopharmaceutical company using its proprietary RADR artificial intelligence ("A.I.") and machine learning (ML) platform to transform the cost, pace, and timeline of oncology drug discovery and development, reported that its Board of Directors has authorized an extension through July 31, 2022 of Lantern’s existing share repurchase program to acquire up to $7 million of the Company’s common stock (Press release, Lantern Pharma, MAR 22, 2022, View Source [SID1234610559]).

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Since the initiation of the share repurchase program in November 2021, a total of 475,157 shares of common stock have been repurchased pursuant to Lantern’s share repurchase program. Total expenditures for share repurchases from the time of initiation of the share repurchase program through March 21, 2022 were approximately $3.4 million, including purchase fees. Lantern is authorized to purchase up to an additional $3.6 million of the Company’s common stock pursuant to the repurchase program. As of December 31, 2021, Lantern had cash, cash equivalents and marketable securities of approximately $70.7 million.

The Company may purchase common stock on the open market, through privately negotiated transactions, or otherwise, in compliance with the rules of the United States Securities and Exchange Commission and other applicable legal requirements. The timing, amount of shares repurchased and prices paid for the stock under the repurchase program will depend on market conditions as well as corporate and regulatory limitations, including blackout period restrictions. The repurchase program does not obligate the Company to acquire any particular amount of shares, and the repurchase program may be suspended or discontinued at any time at the Company’s discretion.

On March 22, 2022 Plus Therapeutics, Inc. (Nasdaq: PSTV) (the "Company"), a clinical-stage pharmaceutical company developing innovative, targeted radiotherapeutics for rare and difficult-to-treat cancers, reported that the first patient has been dosed in the ReSPECT-LM Phase 1/2a dose escalation clinical trial of Rhenium-186 NanoLiposome (186RNL) for the treatment of patients with leptomeningeal metastases (LM) (Press release, Cytori Therapeutics, MAR 22, 2022, View Source [SID1234610558]).

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The investigational drug, 186RNL, is a proprietary nanoscale compound with a unique chelated radioisotope that is administered locally as a single dose via a conventional Ommaya reservoir. Rhenium-186 is a dual energy emitter (beta and gamma) with a short average path length for high precision, low dose rate that is safer for normal tissues, and high radiation density that overwhelms innate DNA repair mechanisms. The dual energy emission allows real time evaluation and monitoring of the 186RNL administration.

The disease target, solid tumor-originating LM, is a deadly and increasingly common central nervous system (CNS) complication potentially from all solid cancer, with breast cancer, lung cancer, gastrointestinal cancer and melanoma being the most common primary sources of LM, with 110,000 cases diagnosed annually in the U.S. LM affects the membranes (meninges) surrounding the brain and spinal cord. There are currently no meaningfully effective Food and Drug Administration-approved treatments.

"The rationale for use of 186RNL in LM patients is scientifically quite attractive, and in clinical practice was very straightforward to administer to our first patient," said Michael Youssef, M.D., Assistant Professor of Neuro-Oncology at University of Texas Southwestern and site Principal Investigator. "Quality of life and survival rates are poor among patients diagnosed with LM from solid tumors. With no standard of care, this represents a true unmet medical need in neuro-oncology."

"LM affects about 10 times the number of patients as glioblastoma but carries a substantially worse prognosis," said Norman LaFrance, M.D., Chief Medical Officer and SVP of Plus Therapeutics. "Initiating treatment in LM patients with 186RNL marks an important milestone for Plus Therapeutics and potentially for the LM patient population."

The ReSPECT-LM trial (NCT05034497) is a multicenter, sequential cohort, open-label, single dose, dose escalation Phase 1/2a study using a modified Fibonacci 3+3 study design. It will evaluate the maximum tolerated dose (MTD), maximum feasible dose (MFD), safety and efficacy of a single administration of 186RNL via intraventricular catheter for LM following standard surgical, radiation and/or chemotherapy treatment. The primary endpoints of the study are the incidence and severity of adverse events/serious adverse events and dose limiting toxicities. Secondary endpoints include overall response rate, duration of response, progression free survival and overall survival.

The ReSPECT-LM Phase 1/2a clinical trial follows preclinical studies in which tolerance to doses of 186RNL as high as 1,075 Gy was shown in animal models with LM with no observed significant toxicity. Treatment led to marked reduction in tumor burden in two animal models of LM.

The Company recently announced the FDA granted Fast Track designation to 186RNL for the treatment of LM. Fast Track designation confers several benefits to the drug development program including 1) more frequent meetings with and written communication from FDA, 2) eligibility for Accelerated Approval and Priority Review, if relevant criteria are met, and 3) Rolling Review, which allows a drug company to submit completed sections of its New Drug Application (NDA) for review by FDA, rather than wait until every section of the NDA is completed before the entire application can be reviewed.

About Leptomeningeal Metastases (LM)

LM is a rare complication of cancer in which the disease spreads to the membranes (meninges) surrounding the brain and spinal cord. LM occurs in approximately 5% of people with cancer and is usually terminal with one-year and two-year survival of just 7% and 3% respectively. LM can originate from solid tumors, primary brain tumors, or hematological malignancies.