On January 4, 2024 OPKO Health, Inc. (NASDAQ: OPK) (the "Company") reported the pricing of its private offering of $200.0 million aggregate principal amount of its Convertible Senior Notes due 2029 (the "Notes") (Press release, Opko Health, JAN 4, 2024, View Source [SID1234639018]). The Company granted the initial purchaser in the offering an option to purchase, within the 13-day period beginning on, and including, the date on which the Notes are first issued, up to an additional $30.0 million aggregate principal amount of the Notes. The sale of the Notes is expected to close on January 9, 2024, subject to customary closing conditions.

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The Notes will be senior unsecured obligations of the Company, will bear interest at a rate of 3.75% per annum, payable semiannually in arrears on January 15 and July 15 of each year, beginning on July 15, 2024, and will mature on January 15, 2029, unless earlier purchased or converted in accordance with their terms. Prior to September 15, 2028, holders of the Notes will have the right to convert their Notes only in certain circumstances and during specified periods and thereafter, will be convertible at the option of the holder at any time prior to the close of business on the business day immediately preceding the maturity date. Conversions of the Notes will be settled in cash, shares of the Company’s common stock ("common stock") or a combination of thereof, at the Company’s election. However, before the Company has available and has reserved the maximum number of shares of the common stock issuable under the Notes, the Company will be required to elect to deliver solely cash or, subject to certain limitations, a combination of cash and shares of the common stock upon conversion. The Notes have an initial conversion rate of 869.5652 shares of common stock per $1,000 principal amount of the Notes (equivalent to an initial conversion price of approximately $1.15 per share of common stock), representing an initial conversion premium of approximately 26.83% above the closing price of $0.9067 per share of the Company’s common stock on January 4, 2024. The conversion rate is subject to adjustment in certain circumstances.

Certain entities affiliated with Phillip Frost, M.D., the Company’s Chairman and Chief Executive Officer, and Jane H. Hsiao, Ph.D., MBA, the Company’s Vice-Chairman and Chief Technical Officer, as well as additional existing holders, have agreed to sign definitive agreements to acquire, in a concurrent private placement, approximately $71.1 million aggregate principal amount of the Company’s Convertible Senior Notes due 2029 (the "Affiliate Notes") in exchange for approximately $71.1 million aggregate principal amount of the Company’s existing 5% convertible promissory notes, inclusive of approximately $5.0 million of accrued but unpaid interest thereon, held by such persons. The Affiliate Notes will constitute part of the same series as the Notes. However, the Affiliate Notes will not initially be fungible with the Notes and will be subject to different transfer restrictions than the Notes. The offering of the Notes is not conditioned upon the closing of the concurrent private placement of Affiliate Notes, but such private placement is conditioned upon the closing of the offering of the Notes.

The Company estimates that the net proceeds from the offering will be approximately $192.5 million (or approximately $221.4 million if the initial purchaser exercises its option to purchase additional notes in full), after deducting fees and estimated offering expenses payable by the Company. The Company expects to use approximately $50.0 million of the net proceeds from the offering of the Notes to repurchase shares of the common stock from purchasers of Notes in privately negotiated transactions effected with or through the initial purchaser or its affiliate. The purchase price per share of the common stock repurchased in such transactions will equal the closing sale price of the Company’s common stock on January 4, 2024, which was $0.9067 per share. These repurchases could increase, or prevent a decrease in, the market price of the common stock or the Notes concurrently with the pricing of the Notes, and may have increased the conversion price for the Notes.

Also, contemporaneously with the pricing of the Notes, the Company entered into separate, privately negotiated transactions with certain holders of the Company’s outstanding 4.50% Convertible Senior Notes due 2025 (the "2025 Convertible Senior Notes") to repurchase for cash approximately $144.4 million aggregate principal amount of such notes. The Company expects to use approximately $146.3 million of the net proceeds from the offering of the Notes and cash on hand to consummate such repurchases. In addition, the Company may, from time to time, repurchase, redeem or otherwise retire additional 2025 Convertible Senior Notes. The terms of the foregoing note repurchases were individually negotiated with certain holders of the 2025 Convertible Senior Notes depending on several factors, including the market price of the common stock and the trading price of the 2025 Convertible Senior Notes at the time of each such repurchase. Such repurchases are not conditioned upon the completion of the offering of the Notes, nor is the completion of the offering of the Notes conditioned upon such repurchases.

The Company intends to use any net proceeds from the offering of the Notes that remain following the foregoing common stock and note repurchases for general corporate purposes.

Any repurchase of the 2025 Convertible Senior Notes, and the potential related market activities by holders of the 2025 Convertible Senior Notes participating in the foregoing note repurchases or as a result of the unwind of their derivative transactions with respect to the common stock, could increase (or reduce the size of any decrease in) the market price of the common stock, which may affect the trading price of the Notes at that time and may have increased the conversion price of the Notes. The Company cannot predict the magnitude of such market activity or the overall effect it will have on the price of the Notes or the common stock.

The Notes and any shares of the common stock issuable upon conversion of the Notes have not been, and will not be, registered under the Securities Act of 1933, as amended (the "Securities Act"), or any other securities laws, and the Notes and any common stock issuable upon conversion of the Notes may not be offered or sold in the United States absent registration under the Securities Act or an applicable exemption from the registration requirements of the Securities Act and other applicable securities laws. The Notes were offered only to persons reasonably believed to be qualified institutional buyers in accordance with Rule 144A under the Securities Act.

This press release does not constitute an offer to sell, or the solicitation of an offer to buy, any securities and shall not constitute an offer, solicitation, or sale in any jurisdiction in which such offer, solicitation or sale would be unlawful. This press release does not constitute an offer to purchase, or notice of redemption, with respect to the 2025 Convertible Senior Notes, and the Company reserves the right to elect not to proceed with the note repurchases described above. This press release does not constitute an offer to repurchase shares of common stock, and the Company reserves the right to elect not to proceed with the common stock repurchases described above.

On January 4, 2024 Adicet Bio, Inc. (Nasdaq: ACET), a clinical stage biotechnology company discovering and developing allogeneic gamma delta T cell therapies for cancer and autoimmune diseases, reported corporate updates and highlighted upcoming priorities for its pipeline programs in 2024 (Press release, Adicet Bio, JAN 4, 2024, View Source [SID1234638999]).

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"In 2024, we aim to make significant strides across our pipeline of differentiated gamma delta T cell therapies through our strategic and disciplined approach," said Chen Schor, President and Chief Executive Officer at Adicet Bio. "The U.S. FDA’s IND clearance of ADI-001 in lupus nephritis marks an important milestone in maximizing the ADI-001 opportunity in the autoimmune therapeutic category that we believe it is ideally suited to address. Clinical data for ADI-001 have demonstrated B-cell depletion that mirrors the B cell depletion by autologous alpha-beta CAR T in academic clinical studies in systemic lupus erythematosus, systemic sclerosis, and idiopathic inflammatory myopathy patients. Given that gamma delta 1 T cells preferentially traffic to organs and tissues, ADI-001 is designed to target and deplete B cells in the periphery, secondary lymphoid organs, kidneys, and other organs, which is highly desirable in autoimmune diseases. ADI-001’s off-the-shelf availability and the favorable safety profile provide the potential for outpatient administration."

Mr. Schor continued: "Our internal research and development efforts are focused in areas where we believe we have a high probability of success and opportunity for significant differentiation. In our ongoing Phase 1 clinical trial of ADI-001 in relapsed or refractory NHL, we have decided to focus our current patient enrollment on the MCL population, which demonstrated the greatest clinical benefit in our June 2023 clinical update. With projected cash runway into the second half of 2025, multiple upcoming milestones, and a disciplined approach, we believe we are well-positioned to advance our pipeline of allogeneic T cell therapy candidates to address substantial unmet needs in oncology and autoimmune diseases."

Program Updates and Expected Milestones for 2024

ADI-001 is an investigational allogeneic gamma delta CAR T cell therapy targeting CD20 for the potential treatment of relapsed or refractory B-cell non-Hodgkin’s Lymphoma (NHL) and autoimmune diseases.

Autoimmune diseases

IND cleared for lupus nephritis. In December 2023, the FDA cleared Adicet’s IND application for ADI-001 in lupus nephritis.
Initiate Phase 1 clinical trial of ADI-001 for the treatment of lupus nephritis in the second quarter of 2024. The Company plans to initiate a Phase 1 clinical trial to assess the safety and efficacy of ADI-001 in lupus nephritis and may provide a clinical update from the trial in the second half of 2024. Adicet expects to expand into additional autoimmune indications in the near future.
Hematologic malignancies

Focus enrollment on MCL patients in ongoing Phase 1 GLEAN study. Adicet will focus on the MCL patient population in the ongoing Phase 1 GLEAN study (at dose level 4), which experienced the greatest clinical benefit in the June 2023 update. While these were early data, an 80% CR rate and 60% 6-month CR rate in late line MCL patients were reported in the June 2023 clinical update, Cmax and exposure by area under the curve (AUC) exceeded that of approved autologous CD19 CAR T therapies, and a favorable safety profile was observed with no significant risk of cytokine release syndrome, immune effector cell associated neurotoxicity syndrome or T-cell malignancies. These initial clinical results, coupled with the potential to dose off-the-shelf in a community setting, support ADI-001 as a potentially attractive therapy for MCL patients. The Company is evaluating the option of advancing ADI-001 to a potentially pivotal study in MCL patients under an accelerated approval pathway.
The Company remains on track to provide an ADI-001 clinical update in the second half of 2024.
ADI-270 is an investigational allogeneic gamma delta CAR T cell therapy targeting CD70 via the CD27-ligand for the treatment of renal cell carcinoma with potential in other solid tumor indications. ADI-270 is designed to home to solid tumors, with a highly specific targeting moiety for CD70 and an armoring technology of TGF beta dominant- negative receptor to address immunosuppressive factors in the tumor microenvironment. Building on gamma delta 1 tissue tropism to solid tumors and three mechanisms of anti-tumor activity (CAR, innate and adaptive), CAR gamma delta 1 T cells may be well positioned to address solid tumors.

Renal cell carcinoma

Plan to file IND for ADI-270 in 2Q 2024. Following positive feedback from a pre-IND meeting with the FDA, the Company remains on track to file an IND application for ADI-270 in the second quarter of 2024.
Financial Outlook

The Company expects cash and cash equivalents on hand as of December 31, 2023, to enable funding for current and planned operations into the second half of 2025.
Webcast/ Conference Call Information

The live webcast of the presentation can be accessed by registering under "Presentations & Events" in the investors section of the Company’s website at View Source Upon registration, all participants will receive a confirmation email with a unique passcode to provide access to the webcast event. To participate via telephone, please join by dialing 888-788-0099 (domestic) or 312-626-6799 (international) and referencing the conference ID 918 2940 8885. An archived replay will be available for 30 days following the presentation. The archived webcast will be available on the Company’s website beginning approximately two hours after the event.

On January 4, 2024 MOMA Therapeutics, a biotechnology company focused on identifying and targeting highly dynamic, difficult to drug targets in cancer and other diseases, reported a strategic collaboration and licensing agreement with Roche (SIX: RO, ROG; OTCQX: RHHBY) (Press release, MOMA Therapeutics, JAN 4, 2024, View Source [SID1234638998]). This partnership provides Roche with access to MOMA’s proprietary KnowledgeBase platform for the identification and prosecution of a certain number of novel drug targets involved in promoting cancer cell growth and survival.

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MOMA’s KnowledgeBase comprises integrated structure-function capabilities, advanced lead-finding technologies and computation-enabled lead optimization. It was built upon the concept that functionally related targets lacking sequence homology still possess three dimensional structural motifs that can be exploited to produce highly impactful therapies. To date, MOMA has utilized this bespoke platform to accelerate drug discovery in the ATPase target class, a class with a high number of genetically validated targets for which industry efforts to identify therapeutically viable drugs have been hampered by the extent of dynamic protein motion.

"Given its deep expertise and global footprint in oncology, Roche represents an ideal collaborator with whom to further advance the application of MOMA’s platform in a way that impacts patients’ lives. The vision for this collaboration was crafted jointly with Roche to enable each party to bring its strengths in pursuit of this shared goal. It also contributes to the long-term sustainability of MOMA’s core focus as we advance our rich pipeline of precision oncology programs to the clinic," said Asit Parikh, M.D., Ph.D., chief executive officer of MOMA.

Through the collaboration, MOMA will receive $66 million as an upfront cash payment and is also eligible to receive discovery, development, and commercialization milestone payments potentially exceeding US$2 billion, as well as tiered royalties. MOMA will be primarily responsible for all activities for selected targets through to development candidate confirmation, whereas Roche will be responsible for IND-enabling activities and clinical development and commercialization. Additionally, if multiple collaboration assets reach pivotal clinical studies, MOMA will receive a right to co-fund late-stage development of one product in exchange for increased royalties in the US on this product.

"We are excited to join forces with MOMA, combining our leadership in oncology with MOMA’s deep expertise in drug discovery for difficult-to-drug and novel targets in oncology. The broader field of cancer dependencies is of high importance for Roche and we are looking forward to further deepening our knowledge and discovering novel targets involved in cancer cell growth and survival leveraging MOMA’s innovative platform," said James Sabry, M.D., Ph.D., global head of pharma partnering, Roche.

"It is exciting to utilize our industry-leading knowledge in how to identify and drug highly dynamic proteins to deliver on a breadth of discovery programs in partnership with Roche," added Peter Hammerman, M.D., Ph.D., chief scientific officer and head of development at MOMA. "Along with bringing two MOMA-owned high-impact programs to the clinic next year, we are making exciting progress towards our goal of addressing key unmet needs for patients living with advanced cancer."

On January 4, 2024 Avistone Biotechnology Co., Ltd. (also referred to as Avistone Biotechnology or Avistone), an innovative biotechnology company focused on precision oncology therapeutics, reported that they had recently completed their Series B financing of 1 billion Chinese yuan (~$140 million USD) (Press release, Avistone Pharmaceuticals, JAN 4, 2024, View Source [SID1234638997]). The Series B financing was jointly led by SDIC CS Capital and IDG Capital, with participation from Yanchuang Capital and Cathay Capital. Existing shareholder Bain Capital continues to make additional investments.

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This round of financing will be used to support clinical research and development of the Avistone pipeline, including both drug monotherapy studies and internal combinations; to accelerate the screening of new molecules; to support clinical studies and expansion in the United States of America; and to support commercialization of PLB1001 (Vebreltinib) in China. In China, Avistone has established a commercial sales and marketing team covering 25 provinces, nearly 1,000 hospitals, and hundreds of commercial companies and retail outlets.

Dr. Hepeng Shi, founder, chairman and CEO of Avistone Biotechnology, said: "We thank our Series B investors for trusting and investing in Avistone. This very important financing will support the commercialization of our recently approved molecule, PLB1001 (Vebreltinib), in MET Exon 14 Skipping Non-Small Cell Lung Cancer (NSCLC) and will provide funding for our pipeline. We will continue to pursue our vision to become a leading biotechnology company with a deep pipeline and focus on innovation. We aspire to be highly trusted by the patients and families that we serve along with the physicians, practitioners, and scientists that we work with."

SDIC states: "We are pleased to lead the B-round financing for Avistone. The Company has demonstrated impressive execution capabilities and has led effective translational medical work. We firmly believe that the company will continue to produce more clinically advanced innovative products in the future. We are committed to collaborating closely with the Avistone team to foster the company’s growth, ultimately benefiting patients and contributing to the advancement of China’s innovative pharmaceutical industry."

IDG Capital noted that, "We believe that the demand for better products is a prevailing trend in the biopharmaceutical industry, and Avistone has consistently aimed for and practiced this goal. Dr. Shi’s team swiftly achieved breakthroughs from 0 to 1 in product development, showcasing strong execution and product layout capabilities. Additionally, we have high expectations for Avistone’s outstanding commercialization capabilities. We believe that in the future, Avistone can achieve more innovative breakthroughs, and IDG Capital is committed to ongoing support, contributing to the advancement of the innovative pharmaceutical industry alongside Avistone."

Jonathan Zhu, Partner and Co-Head of Asia Private Equity at Bain Capital, expressed that "We are delighted to witness Avistone’s breakthroughs in targeted oncology drug development, positioning itself as a leading domestic innovative pharmaceutical enterprise with successful ventures into Class 1 innovative drugs. We have observed the growth and development of Avistone and have strong confidence in the company’s research and development capabilities, execution efficiency, and pipeline layout strategy. Our continued investment in Avistone underscores our belief in Dr. Shi’s leadership and his team’s ability to efficiently develop groundbreaking innovative biopharmaceuticals. This establishes them as a pioneering platform for tumor-targeted drug innovation rooted in China and globally oriented."

On January 4, 2024 Debiopharm (www.debiopharm.com), a privately-owned, Swiss-based biopharmaceutical company aiming to establish tomorrow’s standards of care to cure cancer and infectious diseases, reported that it has entered into a clinical study and collaboration agreement with Repare Therapeutics Inc. ("Repare") (Nasdaq: RPTX), a leading clinical-stage precision oncology company (Press release, Debiopharm, JAN 4, 2024, View Source [SID1234638995]). This clinical collaboration aims to explore the synergy between Debio 0123, a potential best-in-class, brain-penetrant, and highly selective WEE1 inhibitor, and lunresertib, a first-in-class, selective and potent oral, small molecule inhibitor of PKMYT1 with demonstrated anticancer activity.

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"We are delighted to enter into this clinical collaboration with Repare, the leader in PKMYT1 inhibition, to reinforce our commitment to the DDR space with our potential best-in-class WEE1 inhibitor. We believe this synthetic lethality approach will bring an innovative precision medicine therapy to patients"

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Under the clinical study and collaboration agreement, the combination of lunresertib and Debio 0123 will be evaluated in a new arm of Repare’s ongoing global MYTHIC study (NCT04855656) under Repare’s sponsorship. The Phase 1/1b clinical trial is anticipated to initiate in the first half of 2024. Debiopharm and Repare will collaborate on the design of the trial arm for the development of the combination and will share all costs equally. Debiopharm and Repare will each supply their respective drugs, and each retain all commercial rights to their respective compounds, including as monotherapy or as combination therapies.

"We are delighted to enter into this clinical collaboration with Repare, the leader in PKMYT1 inhibition, to reinforce our commitment to the DDR space with our potential best-in-class WEE1 inhibitor. We believe this synthetic lethality approach will bring an innovative precision medicine therapy to patients," said Bertrand Ducrey, CEO of Debiopharm. "This is the first time that Debiopharm has initiated a collaboration to combine two investigational compounds, demonstrating our excitement by the potential of this therapeutic approach in hard-to-treat cancers."

At the AACR (Free AACR Whitepaper)-NCI-EORTC conference held in Boston in October 2023, Repare presented data showing that the combination of lunresertib and Debio 0123 is highly synergistic, and drives rapid and deep tumor regressions (Gallo et al., Poster #A023). Unpublished data independently generated by Debiopharm confirmed the dramatic synergy of the Debio 0123/lunresertib combination in vivo, further supporting the rationale for this clinical collaboration. In addition, several recent preclinical studies published by Repare and its collaborators have demonstrated proof-of-concept for the combination of WEE1 and PKMYT1 inhibition in relevant cancer cell lines and animal models of cancer (Sokhi et al. "Investigating Wee1 and Myt1 combined inhibition as a potential cancer therapeutic strategy", AACR (Free AACR Whitepaper) 2023, Poster #5511; Benada et al., 2023).

"Combining with Debiopharm’s highly selective WEE1 inhibitor is the ideal strategy to further extend our leadership in PKMYT1 inhibitor development," said Lloyd M. Segal, CEO of Repare. "The compelling mechanistic rationale and preclinical data Repare and Debiopharm have each generated for this combination give us confidence in its potential to deliver transformative benefit to patients with high unmet medical need."