On December 5, 2022 Syndax Pharmaceuticals, Inc. (Nasdaq: SNDX), a clinical-stage biopharmaceutical company developing an innovative pipeline of cancer therapies, reported that the U.S. Food and Drug Administration (FDA) has granted Breakthrough Therapy Designation (BTD) for revumenib for the treatment of adult and pediatric patients with relapsed or refractory (R/R) acute leukemia harboring a KMT2A rearrangement (KMT2Ar) (Press release, Syndax, DEC 5, 2022, View Source [SID1234624803]). Revumenib is the Company’s highly selective, oral menin inhibitor.

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"The Breakthrough Therapy Designation underscores revumenib’s potential as a first- and best-in-class therapy to meaningfully change the treatment paradigm for patients with R/R KMT2Ar acute leukemia, whether it presents clinically as acute myeloid leukemia (AML) or acute lymphocytic leukemia (ALL), in adults or children," said Michael A. Metzger, Chief Executive Officer. "Revumenib has the potential, if approved, to be the first drug to address the significant unmet need in KMT2Ar leukemia believed to occur in up to 10% of all acute leukemias, including in approximately 80% of infant acute leukemias. Syndax is committed to bringing revumenib to these patients as quickly as possible and we look forward to working collaboratively with the FDA to expedite a potential approval of revumenib."

The BTD is supported by Phase 1 data from the AUGMENT-101 trial. Ten of 37 patients (27%) with age and phenotype agnostic KMT2Ar acute leukemia treated at doses meeting the protocol defined criteria for the recommended Phase 2 dose (RP2D) and evaluable for efficacy as of the March 2022 data cutoff achieved a complete remission as measured by a CR/CRh. Included in this analysis were patients treated in Arm A (226 and 276 mg q12 hours not receiving a strong CYP3A4 inhibitor) and Arm B (113 and 163 mg q12 hours receiving a strong CYP3A4 inhibitor).

As previously announced, additional data from the Phase 1 portion of the AUGMENT-101 trial will be presented during two oral sessions at the American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting on December 10, 2022. The abstracts (Abstracts #63 and #376) describe data on the 60 patients with R/R mutant NPM1 (n=14) or KMT2A rearranged (MLLr; n=46) acute leukemia that were evaluable for efficacy as of the March 2022 data cutoff date. Additional analyses from the trial that will be presented at the ASH (Free ASH Whitepaper) Annual Meeting indicate a 27% CR/CRh rate at doses meeting the protocol defined criteria for the RP2D in all efficacy evaluable patients (13/48) and in patients with an NPM1 mutation (3/11). There were no discontinuations due to treatment-related adverse events.

The FDA grants BTD to expedite the development and regulatory review of drugs that are intended for serious or life-threatening conditions. The designation is based on preliminary clinical evidence indicating that a drug may demonstrate substantial improvement on at least one clinically significant endpoint over available therapy. BTD affords all of the benefits of the fast track program, eligibility for rolling review and potentially priority review, and additional engagement to facilitate an expedited development plan and regulatory review.

About Revumenib

Revumenib is a potent, selective, small molecule inhibitor of the menin-MLL binding interaction that is being developed for the treatment of KMT2A rearranged, also known as mixed lineage leukemia rearranged or MLLr, acute leukemias including acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML), and NPM1 mutant AML. Revumenib is currently being evaluated in several clinical trials, including the Company’s pivotal AUGMENT-101 Phase 1/2 open-label clinical trial for the treatment of relapsed/refractory (R/R) acute leukemias. Robust clinical activity with durable responses have been reported in the Phase 1 portion of AUGMENT-101. Revumenib was granted Orphan Drug Designation by the U.S. Food and Drug Administration (FDA) and European Commission for the treatment of patients with AML, and Fast Track designation by the FDA for the treatment of adult and pediatric patients with R/R acute leukemias harboring a KMT2A rearrangement or NPM1 mutation.

About KMT2A (MLL) Rearranged Acute Leukemia

Rearrangements of the KMT2A (mixed lineage leukemia or MLL) gene give rise to KMT2Ar acute leukemia known to have a poor prognosis, with less than 25% of adult patients surviving past five years. KMT2A genes produce fusion proteins that require interaction with the protein called menin to drive leukemic cancer growth. Disruption of the menin-KMT2Ar interaction has been shown to halt the growth of KMT2Ar leukemic cells.

KMT2Ar acute leukemia can phenotypically appear as AML, ALL, or mixed phenotype acute leukemia (MPAL) and is routinely diagnosed through currently available cytogenetic or molecular diagnostic techniques. The median overall survival (OS) after standard of care first-line treatment, including intensive chemotherapy and transplant, is less than 1 year and the majority of patients suffer relapse within 5 years. Most R/R patients treated with second-line therapy relapse within the first year. With third line treatment or beyond, only a small percentage of patients achieve complete remission (CR), and the median OS is less than 3 months.

About AUGMENT-101

AUGMENT-101 is a Phase 1/2 open-label trial designed to evaluate the safety, tolerability, pharmacokinetics, and efficacy of orally administered revumenib. The Phase 1 dose escalation portion of AUGMENT-101 was separated into two cohorts based on concomitant treatment with a strong CYP3A4 inhibitor. Arm A enrolled patients not receiving a strong CYP3A4 inhibitor, while Arm B enrolled patients receiving a strong CYP3A4 inhibitor. The Phase 2 pivotal portion of AUGMENT-101 is currently underway. Patients will be enrolled across each of the following trial populations: patients with NPM1 mutant AML, patients with KMT2Ar (MLLr) AML, and patients with KMT2Ar (MLLr) ALL. Discussions with the FDA have confirmed that AUGMENT-101 may potentially serve as the basis for regulatory filings in each patient population. The primary endpoint for each of the trials will be efficacy as measured by complete remission rate (CR + CRh), with key secondary endpoints including duration of response (DOR) and overall survival (OS).

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

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).

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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.

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.

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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.

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.

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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.