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Syndax Pharmaceuticals and Incyte Announce Axatilimab Phase 1/2 Data in Patients with Chronic Graft-Versus-Host Disease Published in the Journal of Clinical Oncology

Syndax Pharmaceuticals, Inc. (Nasdaq: SNDX) and Incyte (Nasdaq: INCY) reported that results from the Phase 1/2 trial of axatilimab, Syndax’s anti-CSF-1R antibody, in patients with recurrent or refractory chronic graft-versus-host disease (cGVHD) following two or more prior lines of therapy, were published in the Journal of Clinical Oncology (Press release, Syndax, DEC 5, 2022, View Source [SID1234624802]).

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A total of 40 patients with refractory disease who received a median of four prior systemic therapies, some of which included ibrutinib, ruxolitinib and belumosudil, were treated in the Phase 1/2 dose escalation trial. Thirty-nine patients were evaluable for response as of the data cutoff. All study participants were treated for a median duration of 29 weeks, with all responding patients treated for a median duration of 38 weeks at the time of data cut-off. Results showed:

Overall response rate by cycle 7 day 1 was 82% (18/22) in the Phase 2 cohort (1mg/kg every two weeks) and 67% (26/39) among all evaluable patients treated in the dose escalation study. Best ORR (complete response + partial response) observed at any point during the study in all patients treated was 69% (27/39).
Median duration of response for Phase 2 responding patients was not reached; 33% of patients experiencing sustained response lasting 20 weeks or longer.
A decrease in glucocorticoids doses was observed in 52% of responding patients.
Responses were observed across a range of organ systems with difficult to treat manifestations such as lung (5/16), skin (5/35), and joints and fascia (19/31).
A clinically meaningful disease improvement using the Lee Symptom Score of at least 7 points was seen in 58% (21/36) of all evaluable patients.
Axatilimab was well tolerated with a favorable safety profile in this refractory population. The most common adverse events were consistent with on-target effects of CSF-1R inhibition. In the Phase 1 cohort, two dose limiting toxicities were reported, both at the 3 mg/kg every two weeks dose. There were no ≥Grade 3 on-target toxicities of CSF-1R blockade seen in the Phase 2 cohort. There was no incidence of cytomegalovirus or other viral reactivation, and no apparent increases in risk for infection. Serious adverse events occurred in 40% (16/40) of patients, with seven (18%) patients discontinuing the study intervention due to adverse events, four (10%) of which were deemed treatment-related.

"We believe axatilimab is well positioned to potentially be a first- and best-in-class anti-CSF-1R antibody for cGVHD," said Kate Madigan, M.D., Chief Medical Officer of Syndax. "The robust, durable responses and multi-organ clinical benefit observed in this Phase 1/2 trial in refractory patients support the potential for axatilimab to serve as an effective intervention in this underserved population."

"The results of this Phase 1/2 dose finding study are very encouraging regarding the ability of axatilimab to provide meaningful clinical responses in chronic GVHD patients that have been refractory to multiple prior therapies" said Carrie Kitko, M.D., Medical Director of the Pediatric Stem Cell Transplant Program at the Vanderbilt-Ingram Cancer Center, and the corresponding author of the Phase 1/2 publication. "Combining both anti-inflammatory and anti-fibrotic effects through the targeting of disease associated macrophages would be particularly exciting for this patient population that would benefit from a reduction in sclerotic and fibrotic manifestations of chronic GVHD. In the past simply stopping further progression of those manifestations was considered a "win", but some of these patients are actually having improvements in joint range of motion and skin tightening."

The article, titled "Axatilimab for chronic graft-versus-host disease after failure of at least two prior systemic therapies: results of a Phase 1/2 study," is available online.

About Chronic Graft-Versus-Host Disease
Chronic graft-versus-host disease, an immune response of the donor-derived hematopoietic cells against recipient tissues, is a serious, potentially life-threatening complication of allogeneic hematopoietic stem cell transplantation which can last for years. Chronic GVHD is estimated to develop in approximately 40% of transplant recipients, and affects approximately 14,000 patients in the U.S.1,2 Chronic GVHD typically manifests across multiple organ systems, with skin and mucosa being commonly involved, and is characterized by the development of fibrotic tissue.3

About Axatilimab
Axatilimab is an investigational monoclonal antibody that targets colony stimulating factor-1 receptor, or CSF-1R, a cell surface protein thought to control the survival and function of monocytes and macrophages. In pre-clinical models, inhibition of signaling through the CSF-1 receptor has been shown to reduce the number of disease-mediating macrophages along with their monocyte precursors, which has been shown to play a key role in the fibrotic disease process underlying diseases such as cGVHD and IPF. Phase 1/2 data of Axatilimab in cGVHD demonstrating its broad activity and tolerability was last presented at the 63rd American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting. Axatilimab was granted Orphan Drug Designation by the U.S. Food and Drug Administration for the treatment of patients with cGVHD and IPF. In September 2021, Syndax and Incyte entered into an exclusive worldwide co-development and co-commercialization license agreement for axatilimab. Axatilimab is being developed under an exclusive worldwide license from UCB entered into between Syndax and UCB in 2016.

Enrollment in the Company’s global pivotal Phase 2 AGAVE-201 Phase 2 study evaluating the efficacy, safety, and tolerability of axatilimab in patients with recurrent or refractory active cGVHD who have received at least two prior lines of systemic therapy is complete, and topline data is expected mid-2023. Additionally, a Phase 1 combination trial of ruxolitinib and axatilimab, led by Incyte, is in preparation and expected to initiate by end of the first quarter of 2023, and a Phase 2b trial of axatilimab in patients with idiopathic pulmonary fibrosis led by Syndax is expected to begin in the fourth quarter of 2022.

For more information about AGAVE-201, visit View Source

Spectrum Pharmaceuticals Announces New Employment Inducement Grants for Commercial Staff

On December 5, 2022 Spectrum Pharmaceuticals (NasdaqGS: SPPI), a biopharmaceutical company focused on novel and targeted oncology therapies, reported that on December 5, 2022, Spectrum’s Board of Directors granted an aggregate of 736,988 inducement restricted stock units ("RSUs") to commercial non-executive employees who were hired specifically for the launch of ROLVEDON (Press release, Spectrum Pharmaceuticals, DEC 5, 2022, View Source [SID1234624799]). The awards were granted under Spectrum’s 2022 Employment Inducement Incentive Award Plan ("Inducement Plan") as employment inducement awards pursuant to Nasdaq Listing Rule 5635(c)(4). The Inducement Plan is used exclusively for the grant of equity awards to individuals who were not previously employees of Spectrum, or following a bona fide period of non-employment, as an inducement material to such individuals’ entering into employment with Spectrum, pursuant to Nasdaq Listing Rule 5635(c)(4).

The RSUs will vest over three years on the first three anniversaries of the grant date, subject to continued service through each applicable vesting date.

Sorrento Announces Positive Phase II Results of PD-L1 Checkpoint Inhibitor IMC-001 Presented at Asian Congress of the European Society for Medical Oncology (ESMO)

On December 5, 2022 Sorrento Therapeutics, Inc. (Nasdaq: SRNE, "Sorrento") reported the results of a Phase II NK/T-cell lymphoma study of IMC-001, a PD-L1 monoclonal antibody licensed to ImmuneOncia Therapeutics, LLC ("ImmuneOncia") (Seongnam, South Korea) (Press release, Sorrento Therapeutics, DEC 5, 2022, View Source [SID1234624798]). ImmuneOncia is a biotechnology company specializing in immuno-oncology drug development, jointly established by Yuhan Corporation of Korea and Sorrento. In addition to IMC-001, ImmuneOncia has a wide range of new products in the pipeline, such as IMC-002, a CD47 antibody, and IMC-201, a bispecific antibody.

The Phase II NK/T-cell lymphoma study was selected for an oral presentation at the Asian Congress of the European Society for Medical Oncology (ESMO Asia 2022) in Singapore on December 4th, 2022. The clinical data demonstrated that in patients with heavily treated NK/T-cell lymphoma, 6 of 10 evaluable patients (60%) not only achieved an objective response, but all 6 patients with an objective response also achieved a complete remission with IMC-001. Additionally, 4 of these 6 patients stayed on treatment for over a year, which provides encouraging indication of long-term IMC-001 treatment safety and durable efficacy.

NK/T-cell lymphoma is a rare cancer that is most prevalent in Asian countries, including China and Korea, and is typically treated with a regimen of radiation and chemotherapy. NK/T-cell lymphoma has a high recurrence rate of 75% within two years. Due to the absence of standard-of-care treatment for relapsed/refractory cases, NK/T lymphoma represents a high unmet medical need and significant market opportunity. To date, no single immuno-oncology drug has obtained approval in this indication.

Professor Won Seog Kim of Samsung Medical Center, the presenter and Principal Investigator of the IMC-001 study, commented, "The complete remission and response rate of 60% of IMC-001 significantly outperformed currently available drugs for the treatment, and very rare adverse events of grade 3 or higher also limit concerns over the side effects, making it a leader among PD-L1 drugs. We expect these results to satisfy the criteria for approval."

Heung Tae Kim, Chief Executive Officer of ImmuneOncia said, "This achievement sets a new standard for the second-line treatment of NK/T-cell lymphoma, which has high unmet needs. ImmuneOncia is preparing additional clinical trials to expand its indications in solid cancer."

Henry Ji, Ph.D., Chief Executive Officer of Sorrento commented, "We expect to leverage these data to create momentum to secure additional partnership and co-development opportunities for IMC-001 in regions with a high incidence of NK/T-cell lymphoma, such as China, as well as in other indications."

IMC-001 is a PD-L1 antibody, a fully human immune checkpoint inhibitor, that serves as the basis of the current immuno-oncology market. This antibody activates the anticancer functions of T cells by strongly inhibiting the binding between PD-1 expressed on T cells and PD-L1 expressed on the surface of cancer cells. Moreover, it can mediate ADCC (antibody-dependent cellular cytotoxicity) against tumor cells, as it maintains the Fc effector function using human IgG1.

Entry into a Material Definitive Agreement

On November 30, 2022, Aura Biosciences, Inc. (the "Company") entered into an underwriting agreement (the "Underwriting Agreement") with SVB Securities LLC, Cowen and Company, LLC and Evercore Group L.L.C, as representatives of the several underwriters named therein (the "Underwriters"), pursuant to which the Company agreed to issue and sell 6,700,000 shares of the Company’s common stock, par value $0.00001 per share (the "Common Stock"), to the Underwriters at a public offering price of $12.00 per share (the "Offering") (Filing, 8-K, Aura Biosciences, DEC 5, 2022, View Source [SID1234624797]). Under the terms of the Underwriting Agreement, the Company also granted the Underwriters an option exercisable for 30 days to purchase up to an additional 1,005,000 shares of Common Stock at the same price per share, which was exercised in full on December 1, 2022. The offering closed on December 5, 2022.

The Company received net proceeds from the Offering, after deducting the underwriting discounts and commissions and estimated offering expenses payable by the Company, of approximately $86.7 million. The Company intends to use the net proceeds from the Offering, together with its existing cash, cash equivalents and marketable securities to advance the clinical development of belzupacap sarotalocan for the treatment of choroidal melanoma and NMIBC, to develop the platform and for general corporate purposes. The Company believes that the net proceeds from this offering, together with its existing cash, cash equivalents and marketable securities, will enable it to fund its operating expenses and capital expenditure requirements into 2025.

The Offering was made pursuant to the Company’s Registration Statement on Form S-3 (File No. 333-268105) (the "Registration Statement"), which was previously filed with the Securities and Exchange Commission on November 1, 2022 and became effective on November 7, 2022, and a related prospectus included in the Registration Statement, as supplemented by a preliminary prospectus supplement dated November 30, 2022 and a final prospectus supplement dated November 30, 2022.

The Underwriting Agreement contains customary representations, warranties and covenants of the Company and also provides for customary indemnification obligations of the Company and the Underwriters, including for liabilities under the Securities Act of 1933, as amended. The representations, warranties and covenants contained in the Underwriting Agreement were made only for purposes of such agreement and as of specific dates and were solely for the benefit of the parties to such agreement. The foregoing summary of the Underwriting Agreement is qualified in its entirety by reference to the Underwriting Agreement, a copy of which is attached hereto as Exhibit 1.1 and incorporated herein by reference.

Goodwin Procter LLP, counsel to the Company, delivered an opinion as to legality of the issuance and sale of the Common Stock in the Offering, a copy of which is attached hereto as Exhibit 5.1 and is incorporated herein by reference.

Iveric Bio Announces Pricing of $300 Million Public Offering of Common Stock

On December 5, 2022 IVERIC bio, Inc. (Nasdaq: ISEE) (the "Company"), reported that the pricing of an upsized underwritten public offering of 13,350,000 shares of its common stock at a price to the public of $22.50 per share, less underwriting discounts and commissions (Press release, Ophthotech, DEC 5, 2022, View Source [SID1234624793]). In addition, in connection with the offering, the Company has granted the underwriters an option for a period of 30 days to purchase up to an additional 2,002,500 shares of its common stock at the public offering price, less underwriting discounts and commissions. All of the shares are being offered by the Company.

The gross proceeds from the offering are expected to be approximately $300.4 million, before underwriting discounts and commissions and offering expenses payable by the Company, and without giving effect to any exercise by the underwriters of their option to purchase additional shares.

Morgan Stanley, BofA Securities, Cowen and Stifel are acting as the book-running managers for the offering. Wedbush PacGrow is acting as lead manager for the offering. The offering is expected to close on or about December 5, 2022, subject to customary closing conditions.

The offering is being made only by means of a prospectus supplement and accompanying prospectus that form a part of an automatically effective registration statement. A final prospectus supplement related to the offering will be filed with the Securities and Exchange Commission (the "SEC") and will be available on the SEC’s website at www.sec.gov. Copies of the final prospectus supplement and the accompanying prospectus relating to the offering may also be obtained, when available, by contacting: Morgan Stanley, 180 Varick Street, 2nd Floor, New York, NY 10014, Attn: Prospectus Department, by telephone: 1-866-718-1649, or by email at [email protected]; BofA Securities, 200 North College Street, 3rd floor, Charlotte, NC (28255-0001), Attn: Prospectus Department, by telephone: 1-800-294-1322, or by email at [email protected]; Cowen and Company, LLC, c/o Broadridge Financial Solutions, 1155 Long Island Avenue, Edgewood, NY 11717, by telephone: 1-833-297-2926, or by email at [email protected]; or Stifel, Nicolaus & Company, Incorporated, Attention: Prospectus Department, One Montgomery Street, Suite 3700, San Francisco, CA 94104, by telephone: 1-415-364-2720, or by email at [email protected].

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