On January 5, 2023 Geron Corporation (Nasdaq: GERN), a late-stage clinical biopharmaceutical company, reported the pricing of an upsized underwritten public offering consisting of 55,876,297 shares of its common stock at a public offering price of $2.45 per share and pre-funded warrants to purchase 25,000,000 shares of its common stock (Press release, Geron, JAN 5, 2023, View Source [SID1234625924]). The pre-funded warrants are being sold at a public offering price of $2.449 per pre-funded warrant. All of the securities in the offering are to be sold by Geron. In addition, Geron has granted the underwriters a 30-day option to purchase up to an additional 12,131,444 shares of its common stock, less underwriting discounts and commissions. The offering is expected to close on or about January 10, 2023, subject to the satisfaction of customary closing conditions.

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The gross proceeds to Geron from this underwritten public offering, before deducting the underwriting discount and other estimated offering expenses, are expected to be approximately $198.1 million. Geron currently intends to use the net proceeds from this public offering, together with its existing cash, cash equivalents, restricted cash and current and noncurrent marketable securities, to fund preparatory activities for the potential U.S. commercial launch of imetelstat in lower risk MDS, and, if approved, to fund the potential U.S. commercial launch of imetelstat. Geron intends to use the remaining proceeds, if any, for working capital and general corporate purposes.

Goldman Sachs & Co. LLC and Stifel are acting as joint book-running managers for the offering. Wedbush PacGrow and Baird are acting as co-lead managers for the offering. B. Riley Securities and Needham & Company are acting as co-managers for the offering.

An automatically effective shelf registration statement on Form S-3 relating to the public offering of the shares of common stock and pre-funded warrants described above was filed with the Securities and Exchange Commission (SEC) on January 4, 2023. A preliminary prospectus supplement and accompanying prospectus relating to and describing the terms of the offering has been filed with the SEC and is available on the SEC’s web site at www.sec.gov. When available, copies of the final prospectus supplement and accompanying prospectus relating to the offering may be obtained from: Goldman Sachs & Co. LLC, at Prospectus Department, 200 West Street, New York, New York 10282, by telephone at 1-866-471-2526 or by email at [email protected]; and Stifel, Nicolaus & Company, Incorporated, Attention: Syndicate, One Montgomery Street, Suite 3700, San Francisco, California 94104, by telephone at 415-364-2720 or by email at [email protected].

This press release does not constitute an offer to sell or the solicitation of an offer to buy any of these securities, nor will there be any sale of these securities in any state or other jurisdiction in which such offer, solicitation or sale would be unlawful prior to the registration or qualification under the securities laws of any such state or other jurisdiction.

On January 5, 2023 Genentech, a member of the Roche Group (SIX: RO, ROG; OTCQX: RHHBY), reported that the U.S. Food and Drug Administration (FDA) has accepted the company’s Biologics License Application (BLA) and granted Priority Review for glofitamab, an investigational CD20xCD3 T-cell engaging bispecific antibody, for the treatment of adult patients with relapsed or refractory (R/R) large B-cell lymphoma (LBCL) after two or more lines of systemic therapy (Press release, Genentech, JAN 5, 2023, View Source [SID1234625923]). LBCL is an aggressive (fast-growing) type of non-Hodgkin’s lymphoma (NHL) and is one of the most prevalent types of blood cancer among adults in the U.S. The FDA is expected to make a decision on approval of this novel cancer immunotherapy by July 1, 2023. If approved, glofitamab would be the first fixed-duration, off-the-shelf CD20xCD3 T-cell engaging bispecific antibody available to treat people with an aggressive lymphoma who have previously received multiple courses of treatment.

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"Unfortunately, people with relapsed or refractory large B-cell lymphoma have a poor prognosis and desperately need additional therapies that are immediately available at the time of relapse," said Levi Garraway, M.D., Ph.D., chief medical officer and head of Global Product Development. "Even for patients whose cancer is rapidly progressing, glofitamab given for a fixed duration has shown impressive efficacy and long-term durability, with patients continuing to experience a complete remission after treatment has concluded."

The BLA is based on positive data from the pivotal Phase I/II NP30179 study, which included patients who had previously received multiple courses of therapy, with 85.1% of patients refractory to their most recent therapy and about one-third (33.1%) having received prior CAR T-cell therapy. Results showed that 40.0% of patients (n=62/155) achieved a complete response (CR; a disappearance of all signs of cancer), and 51.6% (n=80/155) achieved an objective response (OR; the combination of CR and partial response, a decrease in the amount of cancer in their body). The median follow-up time was 13.4 months. Among those who achieved a CR, 73.1% continued to experience a response at 12 months, while the median duration of CR was not reached. The median duration of response was 18.4 months.

An earlier cut-off of data from the Phase I/II study showed that glofitamab given as a fixed-duration treatment resulted in early and durable complete remissions. In this analysis, presented at the 64th American Society of Hematology (ASH) (Free ASH Whitepaper) 2022 Annual Meeting and simultaneously published in the New England Journal of Medicine in December 2022, most patients who had achieved a CR at the end of treatment experienced durable responses. The median CR follow-up from the end of treatment was 11.5 months (95% confidence interval [CI]: 10.5-16.4). Twelve months after the end of treatment with glofitamab, 61% of patients (n=37/61) maintained a CR, 92.6% remained progression-free, and only one patient (n=1/44) experienced disease progression.

The most common adverse event was cytokine release syndrome (CRS), which was generally low grade (48.1% of patients had Grade 1 and 12.3% had Grade 2). Most CRS events were associated with initial administration of glofitamab (in cycle 1). The incidence of Grade 3 or higher CRS was 3.9%, with no Grade 5 events. Only one patient (n=1/155) discontinued glofitamab due to CRS.

The FDA will review the glofitamab BLA under the granted Fast Track Designation. Data from the Phase I/II NP30179 study of glofitamab were submitted for review to the European Medicines Agency, and submissions to additional health authorities worldwide are ongoing.

Glofitamab is part of Genentech’s industry-leading CD20xCD3 T-cell engaging bispecific antibody clinical program, which is the broadest and most advanced in lymphoma. Genentech’s portfolio also includes Lunsumio (mosunetuzumab-axgb), which was granted accelerated approval by the FDA and conditional marketing authorization by the European Commission for the treatment of adults with R/R follicular lymphoma who have received at least two prior systemic therapies.

A robust clinical development program for glofitamab is ongoing, including the Phase III STARGLO trial, evaluating glofitamab in combination with gemcitabine and oxaliplatin (GemOx) versus rituximab in combination with GemOx in patients with second-line plus diffuse large B-cell lymphoma (DLBCL) who are ineligible for autologous stem cell transplant. Additional studies are ongoing to investigate the molecule as a monotherapy and in combination with other medicines for the treatment of patients with B-cell non-Hodgkin’s lymphomas, including DLBCL, mantle cell lymphoma and other blood cancers.

About the NP30179 Study

The NP30179 study [NCT03075696] is a Phase I/II, multicenter, open-label, dose-escalation and expansion study evaluating the safety, efficacy and pharmacokinetics of glofitamab in people with relapsed or refractory diffuse large B-cell lymphoma (DLBCL). Outcome measures include complete response rate by an independent review committee (primary endpoint), overall response rate, duration of response, progression-free survival, safety and tolerability (secondary endpoints).

About Large B-Cell Lymphoma

Large B-cell lymphoma (LBCL) is an aggressive (fast-growing) blood cancer and is one of the most prevalent blood cancers among adults. Diffuse large B-cell lymphoma (DLBCL), a subtype of LBCL, is the most common form of non-Hodgkin’s lymphoma (NHL) and accounts for almost a third of NHL diagnoses. While many patients are responsive to initial treatment, four out of 10 are not cured with the current standard of care, and the majority of patients who require subsequent lines of therapy have poor outcomes.

About Glofitamab

Glofitamab is an investigational CD20xCD3 T-cell engaging bispecific antibody designed to target CD3 on the surface of T cells and CD20 on the surface of B cells. Glofitamab was designed with a novel 2:1 structural format. This T-cell engaging bispecific antibody is engineered to have one region that binds to CD3, a protein on T cells, a type of immune cell, and two regions that bind to CD20, a protein on B cells, which can be healthy or malignant. This dual-targeting brings the T cell in close proximity to the B cell, activating the release of cancer cell-killing proteins from the T cell. A robust clinical development program for glofitamab is ongoing, investigating the molecule as a monotherapy and in combination with other medicines for the treatment of people with B-cell non-Hodgkin’s lymphomas, including diffuse large B-cell lymphoma and other blood cancers.

About Lunsumio (mosunetuzumab-axgb)

Lunsumio is a first-in-class CD20xCD3 T-cell engaging bispecific antibody designed to target CD20 on the surface of B cells and CD3 on the surface of T cells. This dual targeting activates and redirects a patient’s existing T cells to engage and eliminate target B cells by releasing cytotoxic proteins into the B cells. A robust clinical development program for Lunsumio is ongoing, investigating the molecule as a monotherapy and in combination with other medicines, for the treatment of people with B-cell non-Hodgkin’s lymphomas, including follicular lymphoma and diffuse large B-cell lymphoma, and other blood cancers.

Lunsumio U.S. Indication

LUNSUMIO (mosunetuzumab-axgb) is a prescription medicine used to treat adults with follicular lymphoma whose cancer has come back or did not respond to previous treatment, and who have already received two or more treatments for their cancer.

It is not known if LUNSUMIO is safe and effective in children.

The conditional approval of LUNSUMIO is based on response rate. There are ongoing studies to establish how well the drug works.

What is the most important information I should know about LUNSUMIO?

LUNSUMIO may cause Cytokine Release Syndrome (CRS), a serious side effect that is common during treatment with LUNSUMIO and can also be severe or life-threatening.

Get medical help right away if you develop any signs or symptoms of CRS at any time, including:

fever of 100.4°F (38°C) or higher
chills
low blood pressure
fast or irregular heartbeat
tiredness or weakness
difficulty breathing
headache
confusion
feeling anxious
dizziness or light-headedness
nausea
vomiting
Due to the risk of CRS, you will receive LUNSUMIO on a "step-up dosing schedule."

The step-up dosing schedule is when you receive smaller "step-up" doses of LUNSUMIO on Day 1 and Day 8 of your first cycle of treatment
You will receive a higher dose of LUNSUMIO on Day 15 of your first cycle of treatment
If your dose of LUNSUMIO is delayed for any reason, you may need to repeat the step-up dosing schedule
Before each dose in Cycle 1 and Cycle 2, you will receive medicines to help reduce your risk of CRS

Your healthcare provider will check you for CRS during treatment with LUNSUMIO and may treat you in a hospital if you develop signs and symptoms of CRS. Your healthcare provider may temporarily stop or completely stop your treatment with LUNSUMIO, if you have severe side effects.

What are the possible side effects of LUNSUMIO?

LUNSUMIO may cause serious side effects, including:

Neurologic problems. Your healthcare provider will check you for neurologic problems during treatment with LUNSUMIO. Your healthcare provider may also refer you to a healthcare provider who specializes in neurologic problems. Tell your healthcare provider right away if you develop any signs or symptoms of neurologic problems during or after treatment with LUNSUMIO, including:
headache
numbness and tingling of the arms, legs, hands, or feet
dizziness
confusion and disorientation
difficulty paying attention or understanding things
forgetting things or forgetting who or where you are
trouble speaking, reading, or writing
sleepiness or trouble sleeping
tremors
loss of consciousness
seizures
muscle problems or muscle weakness
loss of balance or trouble walking
Serious infections. LUNSUMIO can cause serious infections that may lead to death. Your healthcare provider will check you for signs and symptoms of infection before and during treatment. Tell your healthcare provider right away if you develop any signs or symptoms of infection during treatment with LUNSUMIO, including:
fever of 100.4°F (38°C) or higher
cough
chest pain
tiredness
shortness of breath
painful rash
sore throat
pain during urination
feeling weak or generally unwell
Low blood cell counts. Low blood cell counts are common during treatment with LUNSUMIO and can also be severe. Your healthcare provider will check your blood cell counts during treatment with LUNSUMIO. LUNSUMIO may cause the following low blood cell counts:
low white blood cell counts (neutropenia). Low white blood cells can increase your risk for infection
low red blood cell counts (anemia). Low red blood cells can cause tiredness and shortness of breath
low platelet counts (thrombocytopenia). Low platelet counts can cause bruising or bleeding problems
Growth in your tumor or worsening of tumor related problems (Tumor flare). LUNSUMIO may cause serious or severe worsening of your tumor. Tell your healthcare provider if you develop any of these signs or symptoms of tumor flare during your treatment with LUNSUMIO: tender or swollen lymph nodes, chest pain, cough, trouble breathing, and pain or swelling at the site of the tumor
Your healthcare provider may temporarily stop or permanently stop treatment with LUNSUMIO if you develop severe side effects.

The most common side effects of LUNSUMIO include: tiredness, rash, fever, and headache.

The most common severe abnormal lab test results with LUNSUMIO include: decreased phosphate, increased glucose, and increased uric acid levels.

Before receiving LUNSUMIO, tell your healthcare provider about all of your medical conditions, including if you:

have ever had an infusion reaction after receiving LUNSUMIO
have an infection, or have had an infection in the past which lasted a long time or keeps coming back
have or have had Epstein-Barr Virus
are pregnant or plan to become pregnant. LUNSUMIO may harm your unborn baby. Tell your healthcare provider right away if you become pregnant or think you may be pregnant during treatment with LUNSUMIO
Females who are able to become pregnant:

your healthcare provider should do a pregnancy test before you start treatment with LUNSUMIO you should use an effective method of birth control during your treatment and for 3 months after the last dose of LUNSUMIO are breastfeeding or plan to breastfeed. It is not known if LUNSUMIO passes into your breast milk. Do not breastfeed during treatment and for 3 months after the last dose of LUNSUMIO

Tell your health care provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements.

What should I avoid while receiving LUNSUMIO?

Do not drive, operate heavy machinery, or do other dangerous activities if you develop dizziness, confusion, tremors, sleepiness, or any other symptoms that impair consciousness until your signs and symptoms go away. These may be signs and symptoms of CRS or neurologic problems.

These are not all the possible side effects of LUNSUMIO. Talk to your health care provider for more information about the benefits and risks of LUNSUMIO.

On January 5, 2023 Pacira BioSciences, Inc. (Nasdaq: PCRX), the industry leader in its commitment to non-opioid pain management and regenerative health solutions, reported preliminary unaudited total revenue of $666.8 million for 2022, compared with $541.5 million for 2021, representing an increase of 23.1 percent (Press release, Pacira Pharmaceuticals, JAN 5, 2023, View Source [SID1234625922]). The company’s 2022 revenue includes net product sales of EXPAREL (bupivacaine liposome injectable suspension), ZILRETTA (triamcinolone acetonide extended-release injectable suspension), and the iovera° system. Pacira began recognizing sales of ZILRETTA in November 2021 following the completion of its acquisition of Flexion Therapeutics, Inc.

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"Despite ongoing macroeconomic challenges, Pacira continues to outperform the surgical market with significant adjusted EBITDA and durable cash flows that allow us to self-fund growth opportunities while paying down significant portions of our debt," said Dave Stack, chairman and chief executive officer of Pacira BioSciences. "We ended the year with a strong balance sheet and expect to report adjusted earnings per share of at least $2.50 for 2022, marking our ninth consecutive year of positive adjusted earnings. Further solidifying our financial condition, we prepaid $50 million of outstanding principal under our Term Loan B in December 2022 and we expect to use our strong cash position to make another significant pre-payment in 2023 to further reduce our interest expense. With three safe and unique opioid-sparing commercial assets and multiple near- and long-term opportunities across our portfolio, we believe Pacira is well-positioned for continued growth and value generation in 2023 and beyond."

Fourth Quarter and December 2022 Preliminary Revenue Highlights

EXPAREL net product sales of $138.0 million and $139.9 million for the fourth quarters of 2022 and 2021, respectively, and $47.1 million and $50.9 million for the months of December 2022 and 2021, respectively. EXPAREL continues to outperform a flat surgical market with average daily volumes up 10 percent over December 2021. Average daily volume growth was offset by a lower net selling price primarily due to the company’s implementation of 340B Drug Pricing and other strategic partnerships. Pacira also reports average daily growth rates for EXPAREL to account for differences in the number of selling days per reporting period. EXPAREL average daily sales were 104 percent of the prior year for the fourth quarter of 2022 and 107 percent of the prior year for the month of December 2022. For the fourth quarter, the number of EXPAREL selling days were 61 in 2022, versus 64 in 2021. For the month of December, the number of EXPAREL selling days were 20 in 2022, versus 23 in 2021.
ZILRETTA net product sales of $28.0 million and $12.7 million for the fourth quarters of 2022 and 2021, respectively, and $9.4 million and $8.9 million for the months of December 2022 and 2021, respectively. A portion of ZILRETTA sales in the fourth quarter of 2021 occurred prior to the completion of the company’s acquisition of Flexion in November 2021.
iovera° net product sales of $4.6 million and $4.9 million for the fourth quarters of 2022 and 2021, respectively, and $1.7 million and $2.2 million for the months of December 2022 and 2021, respectively.
Other revenue, including sales of bupivacaine liposome injectable suspension, royalties and collaborative licensing revenue, was $1.4 million and $1.8 million in the fourth quarters of 2022 and 2021 and $1.4 million and $0.7 million for the months of December 2022 and 2021, respectively.

2022 Full-Year Preliminary Revenue Highlights

Full-year EXPAREL net product sales of $536.9 million in 2022, compared with $506.5 million in 2021.
Full-year ZILRETTA net product sales of $105.5 million in 2022, compared with $12.7 million in 2021. The company began recognizing ZILRETTA sales upon completing its acquisition of Flexion in November 2021.
Full-year iovera° net product sales of $15.3 million in 2022, compared with $16.2 million in 2021.
Other revenue, including sales of bupivacaine liposome injectable suspension, royalties and collaborative licensing revenue was $9.1 million in 2022, compared with $6.2 million in 2021.

The company did not provide 2022 revenue or gross margin guidance given the uncertainty around labor shortages, COVID-19, and the pace of recovery for the elective surgery market. To provide greater transparency, the company reported monthly intra-quarter unaudited net product sales for EXPAREL, ZILRETTA, and iovera°. The company is also providing weekly EXPAREL utilization and elective surgery data within its investor presentation, which is accessible at investor.pacira.com. Pacira completed its acquisition of Flexion Therapeutics on November 19, 2021, which added ZILRETTA to its commercial offering.

The financial information included in this press release is preliminary, unaudited, and subject to adjustment. It does not present all information necessary for an understanding of the company’s financial results for the fourth quarter or full year 2022. Pacira expects to report its complete financial results for the fourth quarter and full-year 2022, along with financial guidance for 2023, in the first quarter of 2023.

On January 5, 2023 Fate Therapeutics, Inc. (NASDAQ: FATE), a clinical-stage biopharmaceutical company dedicated to bringing a first-in-class pipeline of induced pluripotent stem cell (iPSC)-derived cellular immunotherapies to patients with cancer and autoimmune disorders, reported that it has declined a proposal from Janssen Biotech, Inc. ("Janssen") for continuation of the collaboration and option agreement between the parties on revised terms and conditions and, as a result, the agreement has been terminated and all collaboration activities will be wound down in the first quarter of 2023 (Press release, Fate Therapeutics, JAN 5, 2023, View Source [SID1234625921]). In addition, the Company has completed a strategic review of its natural killer (NK) cell product pipeline and has elected to focus on advancing its most innovative and differentiated programs, which have a multiplexed-engineered cellular framework of novel synthetic controls designed to promote multi-antigen targeting, increase potency, extend functional persistence, and enable patient dosing with reduced conditioning chemotherapy. The Company ended the fourth quarter with approximately $475 million in cash, cash equivalents, and receivables and, based on its pipeline prioritization and expense reduction, the Company expects to have sufficient financial resources through the end of 2025 to capitalize on its iPSC-derived chimeric antigen receptor (CAR) NK and CAR T-cell programs.

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"We are disappointed that we were not able to align with Janssen on their proposal for continuation of our collaboration, where two product candidates targeting high-value, clinically-validated hematology antigens were set to enter clinical development in 2023," said Scott Wolchko, President and Chief Executive Officer of Fate Therapeutics. "As a consequence, in keeping with the Company’s commitment to develop disruptive product candidates, programs and technologies with the potential to address large, unmet clinical needs, we have prioritized our clinical programs and substantially reduced operating expenses, including taking the difficult and painful step of reducing our workforce, to ensure that we have a three-year cash runway. We are greatly saddened to move in this direction as our employees have continually demonstrated the highest level of dedication and commitment in pioneering iPSC-derived cell therapy for patients with cancer. I want to extend my deepest appreciation to all of our employees for their tremendous efforts and wish those employees who will be departing great success in the future."

"Our second-generation CD19-targeted CAR NK cell program incorporates CD38 knock-out and can be effectively combined with B cell-targeted monoclonal antibody therapy, including those targeting CD20 and CD38, to direct a multi-antigen attack on target cells. This broadens the program’s therapeutic application to include both hematologic malignancies, including non-Hodgkin’s lymphoma and multiple myeloma, and severe autoimmune disorders, and has the potential to enable patient dosing with reduced conditioning chemotherapy. In 2023, we plan to initiate clinical development and assess the potential of this highly-differentiated program with five novel synthetic controls of cell function, rather than commit our resources to an expansive, registrational-directed effort for our FT596 program which does not benefit from certain attributes that we believe are critical for expanded disease application and broad patient reach," continued Mr. Wolchko. "We also expect initial clinical data from high-dose, multi-dose treatment cohorts in multiple myeloma for our FT576 BCMA-targeted CAR NK cell program, which in combination with CD38-targeted monoclonal antibody therapy is designed to enable dual-antigen targeting and to extend functional persistence by selectively depleting activated host immune cells. In addition, we look forward this year to the further emergence of our iPSC-derived CAR T-cell programs for the treatment of hematologic malignancies and solid tumors. Dose and dose schedule optimization is ongoing for FT819, our first iPSC-derived CAR T-cell program, where we continue to assess single-dose and novel split-dose treatment schedules to compare pharmacokinetic, safety, and response profiles for non-Hodgkin’s lymphoma. We also plan to submit an IND application to the FDA for FT825/ONO-8250, our first multiplexed-engineered, CAR T-cell solid tumor program under our collaboration with ONO Pharmaceutical, which incorporates seven novel synthetic controls designed to overcome treatment challenges specific to solid tumors."

NK Cell Programs

First IND Submission Planned in Mid-2023 for Second-generation CD19-targeted CAR NK Cell Program. The Company has applied its unique ability to create multiplexed-engineered iPSC lines to improve upon its first-generation FT596 program, incorporating five novel synthetic controls designed to increase NK cell potency, enhance functional persistence, and reduce or eliminate the need to administer conditioning chemotherapy to patients. The additional features, including the knock-out of CD38, have the potential to significantly improve safety and clinical benefit, facilitate ease of combination with standard-of-care regimens including CD20- and CD38-targeted monoclonal antibody (mAb) therapy, and enable use in the treatment of non-Hodgkin’s lymphoma (NHL), multiple myeloma (MM), and severe autoimmune disorders. The program also incorporates the Company’s proprietary alloimmune defense receptor (ADR) technology for which the Company presented preclinical data at the American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition in December 2022, which data indicated that ADR-armed, iPSC-derived CAR NK cells have the potential to proliferate, functionally persist, and durably kill tumor cells while resisting rejection by allo-reactive immune cells. The Company intends to submit an Investigational New Drug (IND) application to the U.S. Food and Drug Administration (FDA) in mid-2023 to commence a Phase 1 study of its second-generation program in combination with CD20-targeted mAb therapy for the treatment of NHL, including without administration of intensive conditioning chemotherapy to patients.
Ongoing Phase 1 Study of FT576 BCMA-targeted CAR NK Cell Program to Accrue Higher-dose, Multi-dose Treatment Cohorts. At the 2022 ASH (Free ASH Whitepaper) Annual Meeting, the Company presented interim Phase 1 clinical data from the low-dose escalation cohorts of single-dose administration of FT576 as monotherapy and in combination with CD38-targeted mAb therapy for the treatment of MM, which showed encouraging clinical evidence of BCMA-targeted activity in heavily pre-treated patients and a favorable safety profile indicating its potential to be administered in the outpatient setting. Moreover, Phase 1 translational data from the combination arm showed that CD38-positive patient immune cells were rapidly and selectively depleted through the first month of therapy, suggesting that iPSC-derived NK cells incorporating CD38 knock-out, such as FT576, may be combined with CD38-targeted mAb therapy to promote dual-antigen targeting of plasma cells and mitigate the risk of rejection. Preclinical data published in November 2022 in the journal Nature Communications (Cichocki et al. 2022, 13:7341) demonstrated that, while single-dose administration of FT576 was effective at controlling tumor growth in vivo, deeper and more sustained anti-tumor activity was observed through multi-dose administration. Dose escalation assessing multi-dose administration of FT576 as monotherapy and in combination with CD38-targeted mAb therapy is currently ongoing at 300 million cells per dose.

T-cell Programs

Ongoing FT819 Phase 1 Study Assessing Single-dose and Novel Split-dose Treatment Schedules. The landmark clinical trial, which is the first-ever clinical investigation of a T-cell product candidate manufactured from a clonal master iPSC line, is assessing conventional single-dose and novel split-dose treatment schedules of FT819 to compare pharmacokinetics, safety, and efficacy. Dose escalation is currently ongoing in a single-dose treatment regimen at 360 million cells and in a split-dose treatment regimen at 60 million cells per dose. At the 2022 ASH (Free ASH Whitepaper) Annual Meeting, the Company presented interim clinical data from its ongoing Phase 1 study, which showed a favorable safety profile and demonstrated objective responses in heavily pre-treated patients with aggressive large B-cell lymphoma, including in patients who were not eligible for or had previously failed autologous CD19-targeted CAR T-cell therapy.
2023 IND Submission Planned for Multiplexed-engineered CAR T-cell Therapy FT825/ONO-8250. Under the Company’s collaboration with ONO Pharmaceutical Co., Ltd. (ONO), the parties are conducting IND-enabling activities for FT825/ONO-8250, a multiplexed-engineered, iPSC-derived CAR T-cell product candidate targeting human epidermal growth factor receptor 2 (HER2)-expressing solid tumors. The product candidate incorporates seven novel synthetic controls designed to enhance effector cell function and overcome unique challenges in treating solid tumors with cell-based cancer immunotherapies, including cell trafficking, tumor infiltration, and immune cell suppression in the tumor microenvironment. At the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) 37th Annual Meeting held in November 2022, the Company presented preclinical data of FT825/ONO-8250, which highlighted the differentiated targeting profile of the novel HER2-targeted binding domain, functional activity of its synthetic CXCR2 receptor to promote cell trafficking, its synthetic TGFβ receptor to redirect immunosuppressive signals in the tumor microenvironment, and its synthetic interleukin-7 receptor fusion protein to induce T-cell activation. The parties expect to submit an IND application to the FDA in 2023 to commence a Phase 1 study of FT825/ONO-8250 for patients with HER2-positive solid tumors.
Preclinical Development to Focus on Multiplexed-engineered, Multi-antigen Targeted CAR T-cell Programs. The Company’s proprietary iPSC product platform enables the selective design of multiplexed-engineered, CAR T-cell product candidates which incorporate novel synthetic controls of cell function and can deliver multiple mechanisms of action. Through the application of its platform, the Company is developing multiplexed-engineered, multi-antigen targeted CAR T-cell product candidates utilizing its library of novel binding domains targeting hematologic malignancy and solid tumor antigens.

Wind Down of Janssen Collaboration

During the fourth quarter of 2022, the FDA allowed an IND application for a first collaboration product for the treatment of B-cell lymphoma, for which the Company expects to receive a $3 million milestone payment, and Janssen exercised its second commercial option for a collaboration product, for which the Company expects to receive a $10 million milestone payment. As a result of the collaboration’s termination, during the first quarter of 2023, the Company will wind down its activities with Janssen, including discontinuing development of all collaboration products, at the expense of Janssen. As a result of such termination, all licenses and other rights granted pursuant to the agreement terminate; neither party has any right to continue to develop, manufacture or commercialize any collaboration product or use the other party’s materials; and neither party is restricted from independently developing, manufacturing, or commercializing any product, including any product directed to any antigen targeted by a collaboration product.

3-year Operational Runway

The Company ended the fourth quarter of 2022 with unaudited cash, cash equivalents, and receivables totaling approximately $475 million. The Company is reducing its headcount to approximately 220 employees in the first quarter of 2023, and is discontinuing clinical development of its FT516 and FT538 NK cell programs in acute myeloid leukemia, its FT516 and FT596 NK cell programs in B-cell lymphoma, and its FT538 and FT536 NK cell programs in solid tumors. Based on its current operating plan, the Company expects to have sufficient financial resources to fund operations through 2025.

About Fate Therapeutics’ iPSC Product Platform

The Company’s proprietary induced pluripotent stem cell (iPSC) product platform enables mass production of off-the-shelf, multiplexed-engineered cell products that are selectively designed, incorporate novel synthetic controls of cell function, and can deliver multiple mechanisms of therapeutic importance to patients. Human iPSCs possess the unique dual properties of unlimited self-renewal and differentiation potential into all cell types of the body. The Company’s first-of-kind approach combines multiplexed-engineering of human iPSCs with single-cell selection to create clonal master iPSC lines. Analogous to master cell lines used to manufacture biopharmaceutical drug products such as monoclonal antibodies, clonal master iPSC lines are a renewable source for manufacturing multiplexed-engineered cell products which are well-defined and uniform in composition, can be mass produced at significant scale in a cost-effective manner, and can be delivered off-the-shelf to maximize patient reach. As a result, the Company’s platform is uniquely designed to overcome numerous limitations associated with the production of cell therapies using patient- or donor-sourced cells, which is logistically complex and expensive and is subject to batch-to-batch and cell-to-cell variability that can affect clinical safety and efficacy. Fate Therapeutics’ iPSC product platform is supported by an intellectual property portfolio of over 350 issued patents and 150 pending patent applications.

On January 5, 2023 Fusion Pharmaceuticals Inc. (Nasdaq: FUSN), and BWXT Medical Ltd., a subsidiary of BWX Technologies, Inc. (NYSE: BWXT), reported that the companies have entered into a preferred partner agreement for the supply of actinium-225 (Press release, Fusion Pharmaceuticals, JAN 5, 2023, View Source [SID1234625920]). Under the agreement, BWXT Medical will provide predetermined amounts of Fusion’s actinium supply needs at volume-based pricing.

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Actinium-225 is an alpha-emitting isotope used in targeted alpha therapies (TATs) that combine the isotope with specific tumor-seeking targeting vectors to kill cancer cells while minimizing the impact to healthy tissues. There is growing demand for the isotope but a limited number of suppliers who are currently able to produce meaningful quantities of high purity actinium.

Fusion Chief Executive Officer John Valliant, Ph.D., said, "Fusion’s portfolio of clinical-stage targeted alpha therapies is expanding, with three proprietary programs in clinical trials and additional programs advancing under our collaboration with AstraZeneca. Based on emerging clinical data in the literature which show the power of alpha particles over conventional beta emitters, we continue to proactively prioritize access to actinium as a critical component of Fusion’s development plans and we are excited to partner with BWXT Medical. As an established global leader in medical isotope manufacturing and supply with proven ability to produce high purity actinium, BWXT Medical has the necessary infrastructure and shipping logistics capabilities to support both clinical and commercial scale manufacturing and distribution of medical isotopes. This agreement increases our existing actinium supply for both current programs as well as future business development opportunities and partnered programs, diversifies our supply chain, and establishes a relationship to collaborate on longer-term commercial production needs."

BWXT Medical President and Chief Executive Officer Jonathan Cirtain, Ph. D., said, "Excitement for the potential of targeted alpha therapies to treat cancer is growing, and we have made the necessary investments in infrastructure and intellectual property to help meet the increasing global demand for actinium. BWXT Medical is now producing high-purity non-carrier added actinium-225. Fusion is a leading developer of targeted alpha therapies, and we are pleased to work with them as their clinical programs continue to advance."