On September 13, 2022 Cellectar Biosciences, Inc. (NASDAQ: CLRB), a late-stage biopharmaceutical company focused on the discovery, development and commercialization of targeted treatments for cancer, reported the publication of a paper highlighting data from an expansion cohort of the ongoing Phase 2 CLOVER-1 study of iopofosine I-131 ("iopofosine") in relapsed/refractory B-cell malignancies in the September issue of Blood Cancer Journal, a peer-reviewed Nature journal (Press release, Cellectar Biosciences, SEP 13, 2022, View Source [SID1234619494]).

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The paper, entitled "Iopofosine I-131 treatment in late-line patients with relapsed/refractory multiple myeloma post anti-BCMA immunotherapy," showed initial results from the expansion cohort of seven post anti-BCMA immunotherapy quad-class refractory relapsed/refractory multiple myeloma patients with a median of 9 prior therapies. For inclusion in the analysis, patients had to receive a prior anti-BCMA CAR-T, antibody drug conjugate or bispecific antibody therapy. Six participants received the target of ≥60 mCi total administered dose of iopofosine, given as 4 doses over 71 days, while one patient received a total administered dose <60 mCi, and was not included in the analysis.

Initial findings in the population receiving ≥60 mCi total administered dose showed an overall response rate (ORR) of 50% and a minimum of stable disease for all treated patients. At the time of data cutoff, while median overall survival had not been reached, the mean overall survival was 9.1 months. The safety was manageable, with no dosing delays, dose reductions, or treatment discontinuations caused by adverse events. The most common grade 3/4 adverse events were cytopenias (thrombocytopenia (75%) and neutropenia (57%)), which is consistent with previous studies. None of the patients experienced febrile neutropenia, and all cytopenias resolved within the study period.

"The 50% overall response rate in patients from this expansion cohort who had received and failed an average of 9 lines of prior treatment, including many of the newer anti-BCMA therapies, CAR T-cell therapies, bispecific antibodies and antibody drug conjugates is impressive," said James Caruso, president and CEO of Cellectar. "We believe these findings along with data from previous clinical studies demonstrate the potential of iopofosine to broadly treat patients with aggressive hematologic cancers, like multiple myeloma, and less aggressive cancers, like Waldenstrom’s macroglobulinemia, which is currently under evaluation in our WAM Clover-1 pivotal study."

About iopofosine I-131

Iopofosine is a small-molecule Phospholipid Drug Conjugate designed to provide targeted delivery of iodine-131 (radioisotope) directly to cancer cells, while limiting exposure to healthy cells. We believe this profile differentiates iopofosine from many traditional on-market treatments. Iopofosine is currently being evaluated in the CLOVER-WaM Phase 2 pivotal study in patients with relapsed/refractory (r/r) Waldenstrom’s macroglobulinemia (WM), a Phase 2b study in r/r multiple myeloma (MM) patients and the CLOVER-2 Phase 1 study for a variety of pediatric cancers. The U.S. Food and Drug Administration granted iopofosine Fast Track Designation for WM patients having received two or more prior treatment regimens, as well as r/r MM and r/r diffuse large B-cell lymphoma (DLBCL). Orphan Drug Designations (ODDs) have been granted for WM, MM, neuroblastoma, rhabdomyosarcoma, Ewing’s sarcoma and osteosarcoma. Iopofosine was also granted Rare Pediatric Disease Designation (RPDD) for the treatment of neuroblastoma, rhabdomyosarcoma, Ewing’s sarcoma and osteosarcoma. The European Commission granted ODDs for r/r MM and WM.

On September 13, 2022 Abeona Therapeutics Inc. (Nasdaq: ABEO) reported that Vish Seshadri, Chief Executive Officer of Abeona, will participate in a panel discussion at the Cantor Fitzgerald Cell and Genetic Medicines Conference on Thursday, September 15, 2022 (Press release, Abeona Therapeutics, SEP 13, 2022, View Source [SID1234619493]). The panel discussion, entitled, "Late Stage and Commercial Gene & Cell Therapy Warriors: How They Got to/Crossed the Finish Line," is scheduled to begin at 2:30 p.m. ET. The Company will also participate in one-on-one investor meetings at the conference.

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Those interested in attending the panel discussion or requesting a one-on-one meeting with Abeona are encouraged to contact their Cantor Fitzgerald representative.

On September 13, 2022 BeyondSpring Inc. (the "Company" or "BeyondSpring") (NASDAQ: BYSI), a clinical stage global biopharmaceutical company focused on developing innovative cancer therapies to improve clinical outcomes for patients who have a high unmet medical need, reported data from a poster presentation at the ESMO (Free ESMO Whitepaper) Congress 2022 being held September 9-13, 2022, in Paris, France (Press release, BeyondSpring Pharmaceuticals, SEP 13, 2022, View Source;utm_medium=rss&utm_campaign=beyondspring-presents-new-clinical-evidence-of-plinabulin-protection-of-granulocyte-monocyte-progenitor-stem-cells-for-the-prevention-of-chemotherapy-induced-neutropenia-at-the-esmo-congress-2022 [SID1234619487]). The poster includes a new analysis from the Phase 2/3 PROTECTIVE-1 (NCT03102606) and PROTECTIVE-2 (NCT03294577) trials. The data provides evidence of protection of bone marrow granulocyte-monocyte progenitor (GMP) stem cells within 24 hours after chemotherapy based on an evaluation of peripheral immature and mature neutrophil counts.

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"We’re pleased to present mechanistic data demonstrating the effectiveness of plinabulin for the prevention of chemotherapy-induced neutropenia (CIN). The acceptance of this data by ESMO (Free ESMO Whitepaper) provides continued validation of our CIN program and how plinabulin can complement the current standard of care," said Dr. Douglas Blayney, professor of medicine at Stanford University Medical School and global principal investigator for the CIN studies. "We’ve known for a while that there is a ‘gap’ in the first week of a chemotherapy cycle where G-CSF isn’t effective, and patients are left vulnerable to CIN and potentially life-threatening infections. This study shows how plinabulin has a mechanism of action (MOA) that can act within the first 24 hours by increasing the number of important cell types that can protect against potential infection. Plinabulin has continuously demonstrated how it can be a novel tool in the oncologist’s arsenal to potentially improve outcomes for these patients."

Poster Presentation Details

Title: Clinical Evaluation of Plinabulin’s Granulocyte-Monocyte Progenitor (GMP) Stem Cell Effects for the Prevention of Chemotherapy-Induced Neutropenia (CIN)

Presentation #: 1588P

Presenter: Dr. Douglas Blayney, professor of medicine at Stanford University Medical School and global principal investigator for the CIN studies

Peripheral blood counts for mature (segmented) and immature neutrophils, white blood cells (WBCs), red blood cells (RBCs) and platelets were obtained from LabCorp. The blood counts were analyzed before and 24 hours after chemo administration without (control; N=198) or with plinabulin (N=298).
The absolute neutrophil count (ANC) with and without plinabulin was comparable at pre-dose C1D1 (p=0.96) but was significantly higher at 24 hours post-chemo dose with plinabulin vs. control (p<0.0001). At 24 hours post-chemo dose, the mean ANC had increased by 3.2 x 109/L with plinabulin (p<0.0001) whereas the mean ANC had decreased by 0.55 x 109/L with the control (p=0.018) due to the myelosuppressive effect of TAC chemotherapy.
Pre-dose (C1D1), the proportion of patients with a GMP-derived immature cell count value >0 was ~0 for both the plinabulin and control arms. At 24 hours post-chemo, the number of patients with an immature neutrophil count >0 had significantly increased with plinabulin but not with the control (shown in the table below). The proportion of patients with immature cells from all other WBCs and RBCs was ~0 at pre- or post-chemo dose with or without plinabulin.
Proportion of patients with these GMP-derived immature cells: Pre-dose C1D1 plinabulin
ficer at BeyondSpring Pharmaceuticals, added, "Plinabulin, given as a single dose per cycle, has differentiated properties compared to G-CSF, such as a same-day-dosing schedule, no significant bone pain and a rapid onset MOA (within 24 hours), which provides a strong basis for its continued development in CIN prevention. It’s been an honor to work with Dr. Blayney and our team at BeyondSpring to unpack the nuances of what makes plinabulin different from what’s currently available for providers and patients. Plinabulin is a unique novel agent with both CIN prevention and anti-cancer properties. We look forward to sharing further analyses in the CIN program as well as continuing to progress on our work with plinabulin as a potential treatment for non-small cell lung cancer."

About Plinabulin

Plinabulin, BeyondSpring’s lead asset, is a selective immunomodulating microtubule-binding agent, which is a potent antigen presenting cell (APC) inducer that is being developed as an anticancer agent. Plinabulin triggers the release of the immune defense protein, GEF-H1, which leads to two distinct effects: first is a durable anti-cancer benefit due to the maturation of dendritic cells resulting in the activation of tumor antigen-specific T-cells to target cancer cells and the second is a CIN prevention benefit. Plinabulin has single agent anti-cancer activity in a number of cancers including small cell lung cancer (SCLC) and multiple myeloma (MM). Plinabulin also exerts early-onset of action in the prevention of chemotherapy-induced neutropenia (CIN) by boosting the number of hematopoietic stem/progenitor cells (HSPCs).

On September 6, 2022 Omega Therapeutics, Inc. (NASDAQ: OMGA) ("Omega"), a clinical-stage biotechnology company pioneering the first systematic approach to use mRNA therapeutics as a new class of programmable epigenetic medicines by leveraging its OMEGA Epigenomic Programming platform, reported that management will participate in a fireside chat at the H.C. Wainwright 24th Annual Global Investment Conference on Monday, September 12, 2022, at 10 a.m. ET (Press release, Omega Therapeutics, SEP 13, 2022, https://www.prnewswire.com/news-releases/omega-therapeutics-to-participate-in-the-hc-wainwright-24th-annual-global-investment-conference-301617171.html [SID1234619108]).

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A live webcast of the fireside chat will be available on the Investors & Media section of the Company’s website at www.omegatherapeutics.com. An archived replay of the fireside chat will be available on the same website for approximately 90 days.

On September 12, 2022, Alnylam Pharmaceuticals, Inc. (the "Company") reported that priced its private offering of $900.0 million in aggregate principal amount of 1.00% Convertible Senior Notes due 2027 (the "Initial Notes") (Filing, 8-K, Alnylam, SEP 12, 2022, View Source [SID1234619609]). On September 13, 2022, the initial purchasers in such offering exercised their option to purchase an additional $135.0 million in aggregate principal amount of the Company’s 1.00% Convertible Senior Notes due 2027 (the "Additional Notes" and together with the Initial Notes, the "Notes"), bringing the total aggregate principal amount of the Notes to $1,035.0 million. The Notes are the Company’s senior unsecured obligations. The Notes were issued pursuant to an Indenture, dated September 15, 2022 (the "Indenture"), between the Company and The Bank of New York Mellon, as trustee. The Indenture includes customary covenants and sets forth certain events of default after which the Notes may be declared immediately due and payable and sets forth certain types of bankruptcy or insolvency events of default involving the Company after which the Notes become automatically due and payable.

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The Notes will mature on September 15, 2027, unless earlier converted, redeemed or repurchased. The Notes will bear interest from September 15, 2022 at a rate of 1.00% per year payable semiannually in arrears on March 15 and September 15 of each year, beginning on March 15, 2023. Before June 15, 2027, noteholders will have the right to convert their Notes in certain circumstances and during specified periods. From and after June 15, 2027, the Notes will be convertible at the option of the noteholders at any time prior to the close of business on the second scheduled trading day immediately preceding the maturity date. The Company will settle any conversions of Notes by paying or delivering, as applicable, cash shares of the Company’s common stock, par value $0.01 per share (the "Common Stock") or a combination of cash and shares of Common Stock, at the Company’s election.

The conversion rate for the Notes will initially be 3.4941 shares of the Common Stock per $1,000 principal amount of Notes, which is equivalent to an initial conversion price of approximately $286.20 per share of the Common Stock. The initial conversion price of the Notes represents a premium of approximately 35.0% over the $212.00 per share last reported sale price of the Common Stock on The Nasdaq Global Select Market on September 12, 2022. The conversion rate is subject to adjustment under certain circumstances in accordance with the terms of the Indenture.

The Company may not redeem the Notes prior to September 20, 2025. The Company may redeem for cash all or any portion of the Notes (subject to certain limitations), at its option, on or after September 20, 2025 and on or prior to the 21st scheduled trading day immediately preceding the maturity date, if the last reported sale price of the Common Stock has been at least 130% of the conversion price then in effect for at least 20 trading days (whether or not consecutive), including the trading day immediately preceding the date on which the Company provides notice of redemption, during any 30 consecutive trading day period ending on, and including, the trading day immediately preceding the date on which the Company provides notice of redemption at a redemption price equal to 100% of the principal amount of the Notes to be redeemed, plus any accrued and unpaid interest to, but excluding, the redemption date. No sinking fund is provided for the Notes, which means that the Company is not required to redeem or retire the Notes periodically.

A copy of the Indenture and the form of the Notes are attached as Exhibit 4.1 and Exhibit 4.2 hereto, respectively, to this Current Report on Form 8-K and are incorporated herein by reference. The foregoing description is qualified in its entirety by reference to such exhibits.

Capped Call Transactions

On September 12, 2022, in connection with the pricing of the Initial Notes, the Company entered into privately negotiated capped call transactions (the "Base Capped Call Transactions") with certain initial purchasers of the Notes or their respective affiliates and certain other financial institutions (the "Option Counterparties"). On September 13, 2022, in connection with the initial purchasers’ exercise of their option to purchase the Additional Notes, the Company entered into additional privately negotiated capped call transactions with the Option Counterparties (the "Additional Capped Call Transactions," and together with the Base Capped Call Transactions, the "Capped Call Transactions"). The Capped Call Transactions initially cover, subject to customary anti-dilution adjustments, the number of shares of the Common Stock that underlie the Notes. The Capped Call Transactions are expected generally to reduce potential dilution to the Common Stock upon conversion of any Notes and/or offset any potential cash payments the Company is required to make in excess of the principal amount of converted Notes, as the case may be, with such reduction and/or offset subject to a cap. The cap price of the Capped Call Transactions is initially $424.00 per share, which represents a premium of 100.0% over the last reported sale price of the Common Stock on The Nasdaq Global Select Market of $212.00 per share on September 12, 2022, and is subject to certain adjustments under the terms of the capped call transactions. The Company used approximately $118.6 million of the net proceeds from the offering of Notes to pay the cost of the Capped Call Transactions.

The Capped Call Transactions are separate transactions entered into by the Company with the Option Counterparties, and are not part of the terms of the Notes and will not affect any noteholder’s rights under the Notes. Holders of the Notes will not have any rights with respect to the Capped Call Transactions.

The foregoing description of the Capped Call Transactions are qualified in their entirety by the copy of the form of call option transaction confirmation relating to the Capped Call Transactions, which is attached as Exhibit 10.1 hereto and incorporated herein by reference.