On March 14, 2023 Kinnate Biopharma Inc. (Nasdaq: KNTE) ("Kinnate"), a clinical-stage precision oncology company, reported that a clinical trial abstract for its investigational pan-RAF inhibitor exarafenib has been selected for an oral presentation during the Clinical Trials Mini Symposium Session at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) 2023 Annual Meeting, being held April 14-19 in Orlando, Fla (Press release, Kinnate Biopharma, MAR 14, 2023, View Source [SID1234628653]).

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The oral presentation represents the first report of safety and clinical efficacy data from the monotherapy dose escalation portion of KN-8701, an ongoing global Phase 1 clinical trial evaluating exarafenib in patients with BRAF-altered solid tumors and NRAS mutant-positive melanoma.

The company also announced that it has initiated enrollment of patients into the monotherapy dose expansion cohorts of KN-8701 and will discuss the expansion strategy, along with results of the AACR (Free AACR Whitepaper) presentation and additional pipeline updates, during a virtual investor webcast on April 17, 2023 at 5:30 p.m. ET

"Kinnate’s presence at AACR (Free AACR Whitepaper) this year represents the first clinical data release from the company and underscores the rapid progress we are making through our discovery engine for those battling cancer," said Nima Farzan, chief executive officer, Kinnate Biopharma Inc. "We look forward to coming together with the scientific community to share monotherapy results on exarafenib, a novel, potentially first-in-class pan-RAF inhibitor. Our extensive preclinical work shows compelling data for exarafenib as a highly selective pan-RAF with broad potential in cancers that harbor BRAF alterations, including in BRAF Class II and Class III where targeted therapies have had limited success."

Separately, new preclinical data for exarafenib monotherapy and in combination with a MEK inhibitor in human NRAS mutant melanoma models will be presented in a poster session.

Kinnate Presentations at AACR (Free AACR Whitepaper) 2023

Title: A Global Phase 1 Clinical Trial Evaluating Exarafenib Monotherapy (KIN-2787), a Highly Selective Pan-RAF Inhibitor, in BRAF-Altered Solid Tumors and NRAS Mutant Melanoma
Author: Alexander Spira, MD, PhD, FACP, Virginia Cancer Specialists Research Institute
Abstract Number: 9851
Session Category: Clinical Trials Mini Symposium
Session Date and Time: April 17, 2023, 3:35 p.m. – 3:45 p.m. ET
Session Location: Chapin Theater – Convention Center

The AACR (Free AACR Whitepaper) website indicates that clinical trial abstracts will be published on April 14, 2023 at 12:00 p.m. ET, at which time Kinnate will also make the abstract available under the Presentations and Publications section of Kinnate.com. The company intends to present an updated data cut with additional patients and follow-up during the oral presentation on April 17. Kinnate will post the presentation slides on April 17 at the same website.

Title: Exarafenib (KIN-2787) is a Potent, Selective Pan-RAF Inhibitor with Activity in Preclinical Models of BRAF Class II/III Mutant and NRAS Mutant Melanoma
Author: Nichol Miller, PhD
Abstract Number: 4927
Poster Board Number: 5
Session Category: Experimental and Molecular Therapeutics
Session Date and Time: Tuesday April 18, 2023 1:30 p.m. – 5:00 p.m. ET

Kinnate will host an exhibit at the AACR (Free AACR Whitepaper) 2023 Annual Meeting at booth number 1725.

For additional information, visit the AACR (Free AACR Whitepaper) Meeting webpage: View Source

Virtual Investor Webcast Information

Kinnate will host a webcast on Monday, April 17, 2023 at 5:30 p.m. ET. Investors and the general public are invited to listen to a live webcast of the session through the "Investors and Media" section on Kinnate.com or by dialing the U.S. toll free number +1-888-256-1007 and entering confirmation code: 7465233. An archived edition of the session will be available following the event.

About Exarafenib

Exarafenib is an orally administered, potent and selective investigational small molecule pan-RAF inhibitor. Unlike currently available treatments that target only Class I BRAF kinase mutations, exarafenib is designed to target BRAF Class II and Class III alterations, where it has the potential to be a first-line targeted therapy, in addition to covering BRAF Class I alterations, and as a potential treatment for NRAS mutation-positive melanoma.

KN-8701 Clinical Trial Background

KN-8701 is an ongoing, global Phase 1 clinical trial (NCT04913285) evaluating exarafenib in patients with advanced solid tumors harboring BRAF Class I, II and III alterations, and/or who have NRAS mutant melanoma. The trial is enrolling patients at more than 35 sites across the globe. KN-8701 contains a two-part dose escalation: Part A1 evaluates exarafenib as a monotherapy across BRAF alterations and tumor types and Part A2 is evaluating exarafenib in combination with binimetinib, a MEK inhibitor. Part B, the dose expansion phase, is evaluating exarafenib at the recommended dose and schedule in patients with BRAF-altered cancers including lung cancer, melanoma and other solid tumors.

On March 14, 2023 Kezar Life Sciences, Inc. (Nasdaq: KZR), a clinical-stage biotechnology company discovering and developing breakthrough treatments for immune mediated and oncologic disorders, reported financial results for the fourth quarter and year ended December 31, 2022 and provided a business update (Press release, Kezar Life Sciences, MAR 14, 2023, View Source [SID1234628652]).

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"We made tremendous progress in both of our first-in-class programs during 2022," said John Fowler, Kezar’s Co-founder and Chief Executive Officer. "These successes include reporting positive Phase 2 MISSION data with zetomipzomib in lupus nephritis, selecting autoimmune hepatitis as the next indication in that program, making continued progress in our Phase 1 study with KZR-261, and presenting exciting preclinical findings from our Protein Secretion Inhibition Platform. We plan to build on this momentum in 2023, with the initiation of the PALIZADE trial in lupus nephritis patients, launching our PORTOLA trial in autoimmune hepatitis, as well as sharing topline results on the dose escalation portion of our Phase 1 study with KZR-261 in solid tumors. With our strong team and solid balance sheet, we are well positioned to deliver meaningful results across both programs in 2023 and beyond."

Zetomipzomib: Selective Immunoproteasome Inhibitor

PALIZADE – Phase 2b clinical trial of zetomipzomib in patients with active lupus nephritis (LN)

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PALIZADE is a global, placebo-controlled, randomized, double-blind Phase 2b clinical trial evaluating the efficacy and safety of two dose-levels of zetomipzomib in patients with active LN. Target enrollment will be 279 patients, who will be randomly assigned (1:1:1) to receive 30 mg of zetomipzomib, 60 mg of zetomipzomib or placebo subcutaneously once weekly for 52 weeks, in addition to standard background therapy. Background therapy can, but will not be mandated to, include standard induction therapy. Over the initial 16 weeks, there will be a mandatory corticosteroid taper to 5 mg per day or less. End-of-treatment assessments will occur at Week 53, and the end-of-study assessments will occur at Week 57. The primary efficacy endpoint is the proportion of patients who achieve a complete renal response (CRR) at Week 37, including a urine protein-to-creatine ratio (UPCR) of 0.5 or less without receiving rescue or prohibited medications

PORTOLA – Phase 2a clinical trial of zetomipzomib in patients with autoimmune hepatitis (AIH) who have not benefited from standard-of-care treatment (ClinicalTrials.gov: NCT05569759)

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PORTOLA is a randomized, double-blind, placebo-controlled Phase 2a clinical trial evaluating the safety and efficacy of zetomipzomib in patients with AIH that are insufficiently responding to standard of care or have relapsed. The target enrollment will be 24 patients, randomized (2:1) to receive either zetomipzomib or placebo in addition to background corticosteroid therapy for 24 weeks, with a protocol-mandated steroid taper by Week 14. The primary efficacy endpoint will measure the proportion of patients who achieve a complete response measured as normalization of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels with a successful corticosteroid taper by Week 24.
MISSION – Completed Phase 2 clinical trial of zetomipzomib in patients with active LN (ClinicalTrials.gov: NCT03393013)

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In November, Kezar presented positive complete results from the 37-week Phase 2 MISSION clinical trial at the American Society of Nephrology’s (ASN) Kidney Week 2022 and at the American College of Rheumatology (ACR) Convergence 2022. The posters are available to view on the Scientific Publications page of Kezar’s website.
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An abstract featuring Kezar’s post-hoc analysis across LN biopsy classes from the Phase 2 MISSION clinical trial has been selected for presentation at the upcoming National Kidney Foundation (NKF) Spring Clinical Meeting 2023, taking place April 11-15, 2023 in Austin, Texas.
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An abstract featuring Kezar’s complete MISSION Phase 1b/2 results has been selected for oral presentation at the upcoming LUPUS & KCR 2023 meeting, taking place May 17-20, 2023 in Seoul, Korea.
Protein Secretion Inhibition Platform

KZR-261: Broad-Spectrum Sec61 Translocon Inhibitor

KZR-261-101 – Phase 1 clinical trial of KZR-261 in patients with locally advanced or metastatic solid malignancies (ClinicalTrials.gov: NCT05047536)

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The Phase 1 clinical trial of KZR-261 is being conducted in two parts: dose escalation and dose expansion in four tumor-specific solid tumors and one all tumor cohort. The study is designed to evaluate safety and tolerability, pharmacokinetics and pharmacodynamics, identify a recommended Phase 2 dose, and to explore the preliminary anti-tumor activity of KZR-261 in patients with locally advanced or metastatic disease. Kezar plans to initiate the dose expansion study in the second half of 2023.
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The KZR-261 trial is currently enrolling Cohort 6 (27 mg/m2). Previously, Cohort 1 (1.8 mg/m2) through Cohort 4 (12 mg/m2) enrolled a total of 12 patients and completed rapid dose escalation without significant safety concerns. Cohort 5 (18 mg/m2) enrolled six patients, and two patients are currently in the fifth cycle. The Cohort 5 dose-level is approximately equivalent to the minimally effective dose as determined in preclinical anti-tumor studies

To date, KZR-261 has shown dose-proportional exposure and no signs of accumulation or altered pharmacokinetics with repeated dosing. There have been no consistent patterns of safety signals. Kezar plans to report safety and dose escalation data from this trial in the second half of 2023.
KZR-540: Selectively Blocks PD-1 Expression Via Sec61 Translocon Inhibition

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Kezar presented promising preclinical data on KZR-540 at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper)’s (SITC) (Free SITC Whitepaper) 37th Annual Meeting in Boston, MA. KZR-540 demonstrates that the Sec61 translocon can be selectively targeted for specific anti-tumor effects and validates Sec61 inhibition as a platform for additional new chemical entities. The posters are available to view on the Scientific Publications page of Kezar’s website.
Research and Development (R&D) Day Presentation

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Kezar will host a virtual R&D Day on March 15, 2023, at 4:30 pm ET/1:30 pm PT. The event will provide an extensive overview of the Company’s pipeline and review the design of the PALIZADE Phase 2b clinical trial in lupus nephritis. The event will also highlight the recently announced PORTOLA Phase 2a clinical trial, including a presentation on the unmet need in autoimmune hepatitis (AIH) and the AIH treatment landscape from key opinion leader Craig S. Lammert, M.D., Assistant Professor of Medicine at Indiana University and Executive Director of the Autoimmune Hepatitis Association. Kezar will then discuss KZR-261 and developments in the Protein Secretion Platform. To register for this event, please visit the Events & Presentations page of Kezar’s website.
Financial Results

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Cash, cash equivalents and marketable securities totaled $276.6 million as of December 31, 2022, compared to $208.4 million as of December 31, 2021. The increase was primarily attributable to net proceeds from the issuance of common stock, net of cash used in operations to advance clinical-stage programs and preclinical research and development.
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Research and development expenses for the fourth quarter of 2022 increased by $5.1 million to $14.9 million compared to $9.8 million in the fourth quarter of 2021. Full year R&D expenses increased by $12.1 million to $51.0 million in 2022, compared to $38.9 million in 2021. This increase was primarily due to advancing the zetomipzomib clinical program in multiple indications and the KZR-261 clinical program and an increase in stock-based compensation and personnel expenses as a result of an increase in headcount and salaries.
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General and administrative (G&A) expenses for the fourth quarter of 2022 increased by $0.9 million to $5.2 million compared to $4.3 million in the fourth quarter of 2021. Full year G&A expenses increased by $4.4 million to $20.1 million in 2022, compared to $15.7 million in 2021. The increase was primarily due to an increase in stock-based compensation and personnel expenses as a result of an increase in headcount and salaries.
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Net loss for the fourth quarter of 2022 was $18.2 million, or $0.25 per basic and diluted common share, compared to a net loss of $14.2 million, or $0.25 per basic and diluted common share, for the fourth quarter of 2021. Net loss for 2022 was $68.2 million, or $1.01 per basic and

diluted common share, compared to $54.6 million, or $1.04 per basic and diluted common share, in 2021.
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Total shares of common stock outstanding were 68.5 million shares as of December 31, 2022. Additionally, there were outstanding pre-funded warrants to purchase 3.8 million shares of common stock at an exercise price of $0.001 per share, 0.4 million outstanding restricted stock units and options to purchase 9.7 million shares of common stock at a weighted-average exercise price of $8.12 per share as of December 31, 2022.

On March 14, 2023 Karyopharm Therapeutics Inc. (Nasdaq: KPTI), a commercial-stage pharmaceutical company pioneering novel cancer therapies, reported that results from its Phase 1 study evaluating the safety and efficacy of once-weekly selinexor in combination with standard dose ruxolitinib in patients with treatment-naïve myelofibrosis (NCT04562389) have been selected for a poster presentation at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2023, being held April 14-19, 2023 in Orlando, Florida (Press release, Karyopharm, MAR 14, 2023, View Source [SID1234628651]).

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Previous updates of the Phase 1 study showed that the combination of selinexor and ruxolitinib was generally well tolerated, with improvements in spleen and symptom responses and hemoglobin stabilization. Updated efficacy, including ≥35% reduction in spleen volume (SVR35) and ≥50% reduction in symptom scores (TSS50), and safety data will be presented from the 24 treatment-naïve myelofibrosis patients enrolled in this study, all of whom have been followed for at least 24 weeks.

"We remain highly encouraged by the efficacy and safety observed with selinexor in combination with ruxolitinib in patients with treatment-naïve myelofibrosis and look forward to presenting updated data from this Phase 1 study at AACR (Free AACR Whitepaper) 2023. The data underscore the potential importance of XPO1 inhibition in myelofibrosis," said Reshma Rangwala, MD, PhD, Chief Medical Officer of Karyopharm.

The Company plans to hold an investor webcast to discuss the updated results from this study.

Details for the AACR (Free AACR Whitepaper) abstract

Title: A Phase 1, Open-Label, Dose-Escalation Study of Selinexor Plus Ruxolitinib in Patients with Treatment-Naïve Myelofibrosis
Abstract Presentation Number: CT261
Session Title: Phase I Clinical Trials 2
Session Date and Time: Tuesday April 18, 2023, 1:30pm -5:00pm (ET)

About XPOVIO (selinexor)

XPOVIO is a first-in-class, oral exportin 1 (XPO1) inhibitor and the first of Karyopharm’s Selective Inhibitor of Nuclear Export (SINE) compounds to be approved for the treatment of cancer. XPOVIO functions by selectively binding to and inhibiting the nuclear export protein XPO1. XPOVIO is approved in the U.S. and marketed by Karyopharm in multiple oncology indications, including: (i) in combination with Velcade (bortezomib) and dexamethasone (XVd) in patients with multiple myeloma after at least one prior therapy; (ii) in combination with dexamethasone in patients with heavily pre-treated multiple myeloma; and (iii) in patients with diffuse large B-cell lymphoma (DLBCL), including DLBCL arising from follicular lymphoma, after at least two lines of systemic therapy. XPOVIO (also known as NEXPOVIO in certain countries) has received regulatory approvals in various indications in a growing number of ex-U.S. territories and countries, including but not limited to the European Union, the United Kingdom, China, South Korea, Canada, Israel and Taiwan. XPOVIO and NEXPOVIO is marketed by Karyopharm’s partners, Antengene, Menarini, Neopharm and FORUS, in China, South Korea, Singapore, Australia, Hong Kong, Germany, Austria, Israel and Canada.

Please refer to the local Prescribing Information for full details.

Selinexor is also being investigated in several other mid- and late-stage clinical trials across multiple high unmet need cancer indications, including in endometrial cancer and myelofibrosis.

SELECT IMPORTANT SAFETY INFORMATION

Warnings and Precautions

Thrombocytopenia: Monitor platelet counts throughout treatment. Manage with dose interruption and/or reduction and supportive care.
Neutropenia: Monitor neutrophil counts throughout treatment. Manage with dose interruption and/or reduction and granulocyte colony–stimulating factors.
Gastrointestinal Toxicity: Nausea, vomiting, diarrhea, anorexia, and weight loss may occur. Provide antiemetic prophylaxis. Manage with dose interruption and/or reduction, antiemetics, and supportive care.
Hyponatremia: Monitor serum sodium levels throughout treatment. Correct for concurrent hyperglycemia and high serum paraprotein levels. Manage with dose interruption, reduction, or discontinuation, and supportive care.
Serious Infection: Monitor for infection and treat promptly.
Neurological Toxicity: Advise patients to refrain from driving and engaging in hazardous occupations or activities until neurological toxicity resolves. Optimize hydration status and concomitant medications to avoid dizziness or mental status changes.
Embryo–Fetal Toxicity: Can cause fetal harm. Advise females of reproductive potential and males with a female partner of reproductive potential, of the potential risk to a fetus and use of effective contraception.
Cataract: Cataracts may develop or progress. Treatment of cataracts usually requires surgical removal of the cataract.
Adverse Reactions

The most common adverse reactions (≥20%) in patients with multiple myeloma who receive XVd are fatigue, nausea, decreased appetite, diarrhea, peripheral neuropathy, upper respiratory tract infection, decreased weight, cataract and vomiting. Grade 3–4 laboratory abnormalities (≥10%) are thrombocytopenia, lymphopenia, hypophosphatemia, anemia, hyponatremia and neutropenia. In the BOSTON trial, fatal adverse reactions occurred in 6% of patients within 30 days of last treatment. Serious adverse reactions occurred in 52% of patients. Treatment discontinuation rate due to adverse reactions was 19%.
The most common adverse reactions (≥20%) in patients with multiple myeloma who receive Xd are thrombocytopenia, fatigue, nausea, anemia, decreased appetite, decreased weight, diarrhea, vomiting, hyponatremia, neutropenia, leukopenia, constipation, dyspnea and upper respiratory tract infection. In the STORM trial, fatal adverse reactions occurred in 9% of patients. Serious adverse reactions occurred in 58% of patients. Treatment discontinuation rate due to adverse reactions was 27%.
The most common adverse reactions (incidence ≥20%) in patients with DLBCL, excluding laboratory abnormalities, are fatigue, nausea, diarrhea, appetite decrease, weight decrease, constipation, vomiting, and pyrexia. Grade 3–4 laboratory abnormalities (≥15%) are thrombocytopenia, lymphopenia, neutropenia, anemia, and hyponatremia. In the SADAL trial, fatal adverse reactions occurred in 3.7% of patients within 30 days, and 5% of patients within 60 days of last treatment; the most frequent fatal adverse reactions was infection (4.5% of patients). Serious adverse reactions occurred in 46% of patients; the most frequent serious adverse reaction was infection (21% of patients). Discontinuation due to adverse reactions occurred in 17% of patients.
Use In Specific Populations
Lactation: Advise not to breastfeed.

For additional product information, including full prescribing information, please visit www.XPOVIO.com.

To report SUSPECTED ADVERSE REACTIONS, contact Karyopharm Therapeutics Inc. at 1–888–209–9326 or FDA at 1–800–FDA–1088 or www.fda.gov/medwatch.

On March 14, 2023 IO Biotech presenting its corporate presentation (Presentation, IO Biotech, MAR 14, 2023, View Source [SID1234628650]).

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On March 14, 2023 Immunocore Holdings plc (Nasdaq: IMCR) ("Immunocore" or the "Company"), a commercial-stage biotechnology company pioneering the development of a novel class of T cell receptor (TCR) bispecific immunotherapies designed to treat a broad range of diseases, including cancer, autoimmune and infectious diseases, reported that it will present four posters at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2023 commencing on 14 April 2023 (Press release, Immunocore, MAR 14, 2023, View Source [SID1234628649]).

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Poster details

Title: Early ctDNA reduction is associated with better overall survival in the Ph 3 trial of tebentafusp in previously untreated metastatic uveal melanoma

Presenting author: Ryan Sullivan
Session: Liquid Biopsies: Circulating Nucleic Acid and Circulating Tumor Cells 1
Date & time: 16 April 2023, 13:30-17:00 (ET)

Title: Melanoma patients with high and low target-expression can benefit from TCR-CD3 bispecifics through direct and indirect mechanisms of tumor control

Presenting author: Esra Güç
Session: Combination Immunotherapies 2
Date & time: 17 April 2023, 13:30-17:00 (ET)

Title: Long-term survival follow-up of tebentafusp in previously treated metastatic uveal melanoma (mUM)

Presenting author: Joe Sacco
Session: Phase II Clinical Trials 2
Date & time: 18 April 2023, 09:00-12:30 (ET)

Title: Evidence of tumor response in orbital lesions treated with tebentafusp in metastatic uveal melanoma patients

Presenting author: Marcus Butler
Session: Late breaking research: clinical research 1/ Endocrinology
Date & time: 17 April 2023, 13:30-17:00 (ET)