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Arcellx and Kite Announce Strategic Collaboration to Co-Develop and Co-Commercialize Late-Stage Clinical CART-ddBCMA in Multiple Myeloma

On December 9, 2022 Arcellx, Inc. (NASDAQ: ACLX) and Kite, a Gilead Company (NASDAQ: GILD), reported a global strategic collaboration to co-develop and co-commercialize Arcellx’s lead late-stage product candidate, CART-ddBCMA, for the treatment of patients with relapsed or refractory multiple myeloma (Press release, Arcellx, DEC 9, 2022, View Source [SID1234624985]). Multiple myeloma is an incurable disease for most patients and the need remains for effective, safe, and broadly accessible therapies.

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"This collaboration marks a significant achievement for the myeloma field and Arcellx," said Rami Elghandour, Arcellx’s Chairman and Chief Executive Officer. "Combining our potentially best-in-class CART-ddBCMA therapy for multiple myeloma with Kite’s global leadership in cell therapy provides the foundation for us to commercialize our therapy at scale. Most importantly this collaboration is focused on accelerating access for patients in need. The synergies between the two companies are a natural fit. We both bring complementary expertise to the collaboration allowing each company to contribute to the partnership without duplication or competing interests, which is critical for building long-term value."

Currently in Phase 2 clinical development, CART-ddBCMA is an investigational cell therapy product comprising autologous T cells that have been genetically modified to target multiple myeloma. CART-ddBCMA utilizes Arcellx’s novel D-Domain binder. Kite and Arcellx will jointly advance the CART-ddBMCA asset.

"The collaboration with Arcellx enables Kite to expand into a new area of high unmet need and bring a potentially best-in-class cell therapy to help many patients," said Christi Shaw, Chief Executive Officer of Kite. "Cell therapy has proven it can change the way cancer is treated by creating a potentially curative therapy for an individual patient, engineered from their own T cells. To deliver cell therapy globally, and at scale, it requires a highly coordinated, vertically integrated organization from R&D to commercialization to manufacturing, dedicated to the unique needs of this very complex field. The Kite team is excited to engage on this meaningful program in the multiple myeloma field, alongside Arcellx’s talented team."

Upon closing, Arcellx will receive an upfront cash payment of $225 million and $100 million equity investment. Both companies will share development, clinical trial, and commercialization costs for CART-ddBCMA and will jointly commercialize and split U.S. profits 50/50. Outside the US, Kite will commercialize the product and Arcellx will receive royalties on sales. Kite will be responsible for the development and commercialization costs for any product under the collaboration that is not co-commercialized. After completion of the technical transfer, Kite will be responsible for manufacturing.

Terms of the Collaboration

Upfront: Upon closing, Arcellx will receive an upfront cash payment of $225 million and $100 million equity investment from Kite.

Manufacturing: After completion of the technical transfer, Kite will be responsible for manufacturing. Kite will be responsible for all manufacturing expenses associated with commercial readiness.

Development: U.S. and global study costs for the iMMagine-1, iMMagine-2 and future clinical studies for CART-ddBCMA and any other co-commercialized product will be shared 50/50 in the U.S. and 60 to Kite / 40 to Arcellx in the Ex U.S. territory.

U.S. Commercialization: 50/50 profit split for products co-commercialized by Arcellx and Kite; Kite will commercialize all other products and Arcellx will receive low to mid teen royalties.

Ex-U.S. Commercialization: Kite will commercialize the product and Arcellx will receive low to mid-teen royalties on sales.

NextGen, Non-Autologous, and ARC-SparX Programs: Arcellx and Kite to collaborate on next generation autologous and non-autologous programs incorporating ddBCMA. Arcellx to receive an option to co-develop and co-commercialize next generation autologous programs and Kite to receive an option to selected ARC-SparX programs in myeloma.

Bank of America is acting as financial advisor to Kite. Wilson Sonsini Goodrich & Rosati is serving as legal counsel to Arcellx.

The transaction is expected to close in the first quarter of 2023. Closing of the transaction is subject to expiration or termination of the waiting period under the Hart-Scott-Rodino Antitrust Improvements Act and other customary conditions.

Conference Call and Webcast Details

The live webcast and conference call will be accessible under the Events & Presentations in the Investors section of the company’s website www.arcellx.com. To participate in the conference call, dial 1-888-440-3310 (domestic) or 1-646-960-0513 (international) and reference conference ID# 1012518. The archived audio webcast will be available on Arcellx’s website following the call and will be available for 30 days.

About Multiple Myeloma

Multiple Myeloma (MM) is a type of hematological cancer in which diseased plasma cells proliferate and accumulate in the bone marrow, crowding out healthy blood cells and causing bone lesions, loss of bone density, and bone fractures. These abnormal plasma cells also produce excessive quantities of an abnormal immunoglobulin fragment, called a myeloma protein (M protein), causing kidney damage and impairing the patient’s immune function. Multiple myeloma is the third most common hematological malignancy in the United States and Europe, representing approximately 10% of all hematological cancer cases and 20% of deaths due to hematological malignancies. The median age of patients at diagnosis is 69 years with one-third of patients diagnosed at an age of at least 75 years. Because MM tends to afflict patients at an advanced stage of life, patients often have multiple co-morbidities and toxicities that can quickly escalate and become life-endangering.

About CART-ddBCMA

CART-ddBCMA is Arcellx’s BCMA-specific CAR-modified T-cell therapy utilizing the company’s novel binding domain for the treatment of patients with relapsed or refractory multiple myeloma. CART-ddBCMA is currently being investigated in a pivotal Phase 2 study called iMMagine-1. Arcellx’s proprietary binding domains are novel synthetic proteins designed to bind specific therapeutic targets. CART-ddBCMA has been granted Fast Track, Orphan Drug, and Regenerative Medicine Advanced Therapy Designations by the U.S. Food and Drug Administration.

Imugene presents new and first CHECKvacc data at the 2022 San Antonio Breast Cancer Symposium

On December 9, 2022 Imugene Limited (ASX:IMU), a clinical stage immuno-oncology company, reported new and first data from triple negative breast cancer (TNBC) patients in the Phase I CHECKVacc trial has been presented as a poster presentation at the 2022 San Antonio Breast Cancer Symposium (SABC 2022) on 9 December 2022 AEDT in San Antonio, Texas (Press release, Imugene, DEC 9, 2022, View Source [SID1234624966]). Information is also available on the company’s website.

The presentation, titled "Phase I study of intratumoral administration of CF33-hNIS-antiPD-L1 (CHECKvacc) in patients with metastatic triple negative breast cancer", was presented by Dr Yuan Yuan M.D., PhD, Cedars Sinai Medicine, Los Angeles and Dr Jamie Rand M.D., City of Hope, Los Angeles.

Imugene MD & CEO Leslie Chong said: "Phase 1 trials are generally designed to look for safety, tolerability and early response signals to determine the optimal dose for further development. I am encouraged that we are seeing positive signals with correlative biomarker and imaging data at such an early stage of our CHECKVacc Phase I trial."

CF33-hNIS-antiPD-L1 administered by intratumoral injection in patients with metatstatic TNBC is safe and well tolerated at the dose levels tested.

Highlights and results include:

1. From October 2021 to June 2022, 6 patients were enrolled in this ongoing study and received at least 1 dose of CHECKvacc injection at dose level 1 (1 x 10^5 pfu) or dose level

2 (3 x 10^5 pfu). 2. No dose-limiting toxicities were observed. No treatment related adverse events were reported for 6 patients except 1 patient with injection site discoloration.

3. 99mTc SPECT imaging for virus tracking from virus induced replication of the human sodium iodide (hNIS) transgene shows enhancement in 4/6 (67%) patients in the first 2 dose levels. Enhancement was greater in patients with injection of nodal disease compared to dermal metastasis.

4. SPECT imaging of patient COH-004 (DL-2) on C1D8 showed significant enhancement of injected lymph node.

5. Baseline and on-treatment tumor biopsies of patient COH-004 using spatial immune profiling showed an increase in PD-L1 positive cells following treatment with CHECKVacc, demonstrating immune activation and tumor microenvironment changes in association with response to therapy. IMUGENE LIMITED ACN 009 179 551 2

Taken together, these data support further evaluation of CHECKVacc in TNBC. CF33-hNIS-antiPDL1 is an immune checkpoint inhibitor armed chimeric vaccinia poxvirus from the lab of CF33 inventor Professor Yuman Fong, Chair of Sangiacomo Family Chair in Surgical Oncology at City of Hope, one of the largest cancer research and treatment organizations in the United States, and a noted expert in the oncolytic virus field.

Oncolytic viruses (OVs) are designed to both selectively kill tumour cells and activate the immune system against cancer cells, with the potential to improve clinical response and survival.

Full study details can also be found on clinicaltrials.gov under study ID: NCT05081492

Replimune Announces Pricing of Public Offering

On December 8, 2022 Replimune Group, Inc. (Nasdaq: REPL), a clinical stage biotechnology company pioneering the development of a novel class of tumor-directed oncolytic immunotherapies, reported the pricing of its public offering of 5,374,486 shares of its common stock at a public offering price of $23.50 per share (Press release, Replimune, DEC 9, 2022, View Source [SID1234624958]). In addition, in lieu of common stock to certain investors, Replimune reported the pricing of its public offering of pre-funded warrants to purchase 4,200,000 shares of its common stock at a purchase price of $23.4999 per pre-funded warrant, which equals the public offering price per share of the common stock less the $0.0001 per share exercise price of each pre-funded warrant. The aggregate gross proceeds from the offering are expected to be approximately $225 million, before deducting the underwriting discounts and commissions and offering expenses payable by Replimune. All securities in the offering are being offered by Replimune. In addition, Replimune has granted the underwriters a 30-day option to purchase up to an additional 1,436,172 shares of its common stock from Replimune at the public offering price, less the underwriting discounts and commissions. The offering is expected to close on December 13, 2022, subject to the satisfaction of customary closing conditions.

J.P. Morgan Securities LLC, SVB Securities LLC, Piper Sandler and BMO Capital Markets Corp. are acting as joint book-running managers for the offering.

A preliminary prospectus supplement relating to and describing the terms of the offering were filed with the Securities and Exchange Commission (the "SEC") on December 7, 2022. The final prospectus supplement relating to the offering will be filed with the SEC. Copies of the final prospectus supplement and the accompanying prospectus relating to the offering may be obtained, when available, by visiting EDGAR on the SEC website at www.sec.gov or from J.P. Morgan Securities LLC, Attention: Broadridge Financial Solutions, 1155 Long Island Avenue, Edgewood, NY 11717, by telephone at (866) 803-9204, or by e-mail at [email protected]; SVB Securities LLC, Attention: Syndicate Department, 53 State Street, 40th Floor, Boston, MA 02109, by telephone at 1-800-808-7525, ext. 6105, or by email at [email protected]; Piper Sandler, Attention: Prospectus Department, 800 Nicollet Mall, J12S03, Minneapolis, MN 55402, by telephone at (800) 747-3924, or by email at [email protected]; BMO Capital Markets Corp., Attention: Equity Syndicate Department, 151 W 42nd Street, 32nd Floor, New York, NY 10036, by telephone at (800) 414-3627, or by email at [email protected]. The final terms of the offering will be disclosed in a final prospectus supplement to be filed with the SEC.

The securities described above are being offered by Replimune pursuant to its shelf registration statement on Form S-3, including a base prospectus, that was previously filed by Replimune with the SEC on June 23, 2022 and declared effective by the SEC on July 27, 2022. This press release shall not constitute an offer to sell or the solicitation of an offer to buy, nor shall there be any sale of these securities, in any state or jurisdiction in which such an offer, solicitation or sale would be unlawful prior to registration or qualification under the securities laws of any such state or jurisdiction.

iOnctura initiates Phase Ib pancreatic cancer trial of next-generation autotaxin inhibitor IOA-289

On December 8, 2022 iOnctura SA a clinical-stage biotech developing selective cancer therapies against targets that play critical roles in multiple tumor survival pathways, reported the first patient has been dosed in a Phase Ib clinical trial of IOA-289 in metastatic pancreatic cancer (Press release, iOnctura, DEC 8, 2022, View Source [SID1234640235]).

"We are excited to progress clinical development of our autotaxin (ATX) inhibitor IOA-289, the second most advanced product in our pipeline," said Catherine Pickering, PhD, CEO of iOnctura. "Our preclinical research has uncovered a central role for ATX as a tumor survival factor, especially in highly fibrotic malignancies such as pancreatic, liver, colorectal, ovarian and breast cancers. To our knowledge, this is the first time an ATX inhibitor will be investigated in cancer patients. The learnings from this study will serve as a prototype to explore the therapeutic potential of IOA-289 in further fibrotic cancers."

The Phase Ib AION-02 study (NCT05586516) is a dose-escalation study of IOA-289 in combination with standard-of-care gemcitabine/nab-paclitaxel chemotherapy in first-line metastatic pancreatic cancer. Patients will be dosed with IOA-289 monotherapy for 7 days before commencing combination treatment of IOA-289 and chemotherapy.

Fibrotic cancers, including pancreatic cancer, are characterized by the deposition of thick layers of extracellular matrix containing collagen fibers and pro-tumorigenic factors. This microenvironment impedes the entry of immune cells and drugs, making the tumors difficult to treat.

"IOA-289 is an orally dosed small molecule that has been shown preclinically to have a multi-pronged approach to treating cancer, acting directly to prevent proliferation of tumor cells and indirectly to potentiate the actions of the immune system and chemotherapy in the fibrotic microenvironment." said David Brindley, Professor of Biochemistry, University of Alberta, and member of iOnctura’s clinical advisory board. "We hypothesize that the lead-in of IOA-289 will reduce the expression of collagen and other pro-tumorigenic secreted factors rendering the tumor microenvironment susceptible to chemotherapy and unveiling the tumor to the immune system."

The trial’s primary endpoint is to evaluate the safety and tolerability of the ascending doses of IOA-289. Secondary endpoints include biomarker changes and efficacy endpoints. The trial will be conducted in sites in Italy and the UK. The principal investigators of the trial are Professor Davide Melisi, University of Verona, Professor Michele Maio, University of Siena and Professor Jeff Evans, University of Glasgow.

IOA-289 is the first autotaxin (ATX) inhibitor in clinical development for cancer. It is an oral small molecule non-competitive inhibitor with novel binding chemistry and a safe clinical profile. It has been shown that inhibiting ATX with IOA-289 directly prevents the proliferation of cancer cells1. Furthermore, IOA-289 interrupts resistance to cancer therapy by reducing fibrotic scar tissue, unveiling the tumor and enabling the immune system to recruit infiltrating lymphocytes into the tumor2. Thanks to this multi-pronged mode of attack, IOA-289 reduced tumor burden in mouse pancreatic cancer models1.

Pancreatic cancer (PDAC): Pancreatic ductal adenocarcinoma (PDAC) is the most common form of pancreatic cancer accounting for approximately 90% of cases. PDAC has a poor prognosis, with less than 5% of patients surviving beyond five years after diagnosis. There are over 50,000 diagnoses of pancreatic cancer each year in the United States and over 65,000 in the EU5.

Autolus Therapeutics to receive $70 million in milestone payments from Blackstone Life Sciences

On December 8, 2022 Autolus Therapeutics plc (Nasdaq: AUTL), a clinical-stage biopharmaceutical company developing next-generation programmed T cell therapies, reported that Blackstone Life Sciences (‘Blackstone’) has committed to make two pre-agreed milestone payments of $35m each to Autolus, totaling $70m (Press release, Autolus, DEC 8, 2022, View Source [SID1234625453]). The milestones are expected to be recognized in Autolus’ Q4 2022 cash balance.

The first Blackstone milestone of $35m is being paid earlier than anticipated as a result of the joint steering committee’s review of Autolus’ interim analysis of pivotal FELIX Phase 2 clinical trial of obecabtagene autoleucel (obe-cel) in relapsed/refractory (r/r) adult Acute Lymphoblastic Leukemia (ALL). The study has met its primary endpoint, the details of which have been announced in a separate press release today.

The second Blackstone milestone of $35m is a pre-agreed manufacturing milestone as a result of completion of planned activities demonstrating the performance and qualification of Autolus’ obe-cel’s manufacturing process.

"Receiving these two $35m milestone payments highlights the continuing strength and collaborative nature of our partnership with Blackstone," said Dr. Christian Itin, CEO of Autolus. "We are delighted to have demonstrated the potential merits of obe-cel’s clinical profile and our evolving robust manufacturing process to the Blackstone team, and look forward to continued progress together as we focus on our goal of submitting a Biologics License Application (BLA) to the U.S. Food and Drug Administration (FDA) by the end of 2023."

"We are pleased with Autolus’ progress —we continue to believe obe-cel has the potential to become a transformative therapy for relapsed/refractory adult ALL patients," said Nicholas Simon, Senior Managing Director with Blackstone Life Sciences. "Our investments in these next generation cell therapies with Autolus exemplifies our conviction in the quality and promise of the life sciences sector in the UK."

As previously announced, Autolus and Blackstone entered into a strategic collaboration and financing agreement in November 2021, whereby funds managed by Blackstone agreed to provide up to $250 million in equity and product financing to support Autolus’ advancement of obe-cel, its CD19 CAR T cell investigational therapy product candidate, as well as next generation product candidates of obe-cel in B-cell malignancies.