Corporate Overview

On January 5, 2024 AnaptysBio presented its corporate presentation (Presentation, AnaptysBio, JAN 5, 2024, View Source [SID1234639004]).

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ADC Therapeutics Provides Business Updates

On January 4, 2024 ADC Therapeutics reported business updates (Press release, ADC Therapeutics, JAN 4, 2024, View Source [SID1234642026]).

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"During 2023, we took a number of decisive actions to help position the Company for success in 2024 and beyond. We prioritized our pipeline, strengthened our organization and implemented a disciplined capital allocation model to generate cost efficiencies," said Ameet Mallik, Chief Executive Officer of ADC Therapeutics. "We believe we are starting to see signs of the commercial turnaround. We are also encouraged to see positive initial signals in the LOTIS-7 trial of ZYNLONTA in combination with bispecifics as well as early signs of antitumor activity in the Phase 1b trial of ADCT-601. We now expect our cash runway to extend into the fourth quarter of 2025 and believe we are on a path to unlock the substantial value in the Company."

Recent Highlights and Developments

ZYNLONTA (loncastuximab tesirine-lpyl)

ZYNLONTA net sales for the fourth quarter of 2023 are expected to be approximately $16.5 million.
The Phase 1 LOTIS-7 trial of ZYNLONTA in combination with bispecifics glofitamab or mosunetuzumab for the treatment of patients with diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL) and marginal zone lymphoma (MZL) is actively enrolling patients. The dose-limiting toxicity (DLT) period has been cleared for the first dosing level of ZYNLONTA 90 µg/kg in both arms, and there have been no discontinuations due to adverse events (AEs). To date, each of the first five patients eligible for assessment in this dosing level has shown a response (partial response or complete response) at first scan.​
An oral presentation at the American Society of Hematology (ASH) (Free ASH Whitepaper) 2023 Annual Meeting from the University of Miami investigator-initiated trial exploring ZYNLONTA in combination with rituximab in high-risk relapsed or refractory FL indicated a best overall response rate of 96.3% and a complete response rate of 85.2%​. After a median follow-up of 9.7 months, the median progression-free survival (PFS) was not reached, and the 12-month PFS was 92.3%​. The majority of AEs were grade 1. Grade 3 AEs included neutropenia (n=2; 6.2%), and one case each (3.1%) of hyperglycemia, increased ALT, fatigue, dyspnea and skin infection. Neutropenia was the only grade 4 AE (n=1; 3.1%).
Pipeline

ADCT-601 (targeting AXL): In the Phase 1b trial, the maximum-tolerated dose has been reached, and the study is currently in dose optimization. There have been early signs of antitumor activity in both monotherapy and in combination. The dose-optimization/ expansion phase is comprised of a monotherapy arm including patients with sarcoma, pancreatic cancer and AXL-expressing non-small cell lung cancer (NSCLC) and a combination arm with gemcitabine in patients with sarcoma and pancreatic cancer.
ADCT-901 (targeting KAAG1): The Company has decided to discontinue this program due to limited signs of efficacy in the dose escalation phase and to reallocate capital to prioritized programs.
ADCT-602 (targeting CD22): Dose escalation and expansion in the Phase 1 trial in collaboration with MD Anderson Cancer Center for patients with relapsed or refractory acute lymphoblastic leukemia is progressing, and additional clinical trial sites are being added to accelerate enrollment.
Early-stage pipeline: The Company is advancing a portfolio of investigational ADCs including those targeting Claudin-6, NaPi2b and PSMA. These candidates utilize exatecan with a novel hydrophilic linker as a highly potent and differentiated payload.
Balance Sheet
The Company ended the fourth quarter of 2023 with cash and cash equivalents of ~$278.5 million.

Guidance
The Company expects the following based on its current business plan:

Decrease in total operating expenses expected in full year 2023 and 2024 as compared to 2022
Cash runway expected into 4Q 20252 (previously: mid-2025)
Expected Milestones in 2024

ZYNLONTA

Achieve commercial brand profitability in 2024
LOTIS-5: Complete enrollment in 2024
LOTIS-7: Additional safety and efficacy data from the dose-escalation and dose-expansion portions of the Phase 1 study in 2024
Pipeline

ADCT-601 (targeting AXL)

Additional data updates from the Phase 1 study in patients with sarcoma, pancreatic cancer and NSCLC in 2024
ADCT-602 (targeting CD22)

Additional data from Phase 1 study in 2024
Please refer to the Company’s Form 8-K and accompanying presentation filed with the Securities and Exchange Commission today for additional information.

About ZYNLONTA (loncastuximab tesirine-lpyl)

ZYNLONTA is a CD19-directed antibody drug conjugate (ADC). Once bound to a CD19-expressing cell, ZYNLONTA is internalized by the cell, where enzymes release a pyrrolobenzodiazepine (PBD) payload. The potent payload binds to DNA minor groove with little distortion, remaining less visible to DNA repair mechanisms. This ultimately results in cell cycle arrest and tumor cell death.

The U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA) have approved ZYNLONTA (loncastuximab tesirine-lpyl) for the treatment of adult patients with relapsed or refractory (r/r) large B-cell lymphoma after two or more lines of systemic therapy, including diffuse large B-cell lymphoma (DLBCL) not otherwise specified (NOS), DLBCL arising from low-grade lymphoma and also high-grade B-cell lymphoma. The trial included a broad spectrum of heavily pre-treated patients (median three prior lines of therapy) with difficult-to-treat disease, including patients who did not respond to first-line therapy, patients refractory to all prior lines of therapy, patients with double/triple hit genetics and patients who had stem cell transplant and CAR-T therapy prior to their treatment with ZYNLONTA. This indication is approved by the FDA under accelerated approval and in the European Union under conditional approval based on overall response rate and continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial. Please see full prescribing information including important safety information about ZYNLONTA at www.ZYNLONTA.com.

ZYNLONTA is also being evaluated as a therapeutic option in combination studies in other B-cell malignancies and earlier lines of therapy.

OPKO Health Announces Pricing of Private Offering of $200 Million Convertible Senior Notes Due 2029

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.

Adicet Provides Corporate Update and Highlights Strategic Priorities for 2024

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.

MOMA Therapeutics Announces Five-Year Discovery Collaboration with Roche Focused on Critical Cancer Dependencies

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."