On December 17, 2021, Oncternal Therapeutics, Inc. ("Oncternal") reported that it entered into an Open Market Sale AgreementSM (the "Sale Agreement") with Jefferies LLC (the "Agent"), pursuant to which Oncternal may offer and sell shares of Oncternal’s common stock having an aggregate offering price of up to $50,000,000 from time to time, in "at the market" offerings through the Agent (Filing, 8-K, Oncternal Therapeutics, DEC 17, 2021, View Source [SID1234597410]). Sales of the shares of common stock, if any, will be made at prevailing market prices at the time of sale, or as otherwise agreed with the Agent. The Agent will receive a commission from Oncternal of 3.0% of the gross proceeds of any shares of common stock sold under the Sale Agreement.

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Oncternal is not obligated to sell, and the Agent is not obligated to buy or sell, any shares of common stock under the Sale Agreement. No assurance can be given that Oncternal will sell any shares of common stock under the Sale Agreement, or, if it does, as to the price or amount of shares of common stock that it sells or the dates when such sales will take place.

In the Sale Agreement, Oncternal agreed to indemnify the Agent against certain liabilities, including under the Securities Act of 1933, as amended, or to contribute payments that the Agent may be required to make because of such liabilities.

The shares of common stock sold pursuant to the Sale Agreement will be offered pursuant to a shelf registration statement on Form S-3 (File No. 333-254985), which became effective on April 15, 2021. Oncternal filed a prospectus supplement with the U.S. Securities and Exchange Commission on December 17, 2021 in connection with the offer and sale of shares of Oncternal’s common stock pursuant to the Sale Agreement.

A copy of the Sale Agreement is attached as Exhibit 1.1 hereto and is incorporated herein by reference. The foregoing description of the Sale Agreement does not purport to be complete and is qualified in its entirety by reference to the full text of the Sale Agreement.

A copy of the opinion of Latham & Watkins LLP relating to the validity of the shares of common stock that may be sold pursuant to the Sale Agreement is filed herewith as Exhibit 5.1.

On December 17, 2021 Karyopharm Therapeutics Inc. (Nasdaq: KPTI), a commercial-stage pharmaceutical company pioneering novel cancer therapies, reported that its partner, Antengene Corporation (Antengene), has been granted conditional approval for marketing by the China National Medical Products Administration (NMPA) for XPOVIO (selinexor), a first-in-class, oral selective inhibitor of nuclear export (SINE) compound, in combination with dexamethasone in patients with relapsed or refractory multiple myeloma who have received prior therapies and whose disease is refractory to at least a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody (Press release, Karyopharm, DEC 17, 2021, View Source [SID1234597370]). Antengene has exclusive development and commercialization rights to selinexor in China and certain Asia Pacific countries.

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This conditional approval was based on the global Phase 2 STORM trial as well as results from Antengene’s Phase 2 MARCH trial in China, which evaluated the efficacy and safety of selinexor plus dexamethasone in patients with relapsed/refractory multiple myeloma. The ongoing, randomized Phase 3 BENCH trial evaluating selinexor in combination with bortezomib and low-dose dexamethasone will serve as the confirmatory trial.

"There is no cure for multiple myeloma, and over time, patients stop responding to available treatments," said Richard Paulson, President and Chief Executive Officer of Karyopharm. "The approval of XPOVIO in China offers patients with relapsed multiple myeloma a new therapeutic option and the first in a new class of therapeutics, to improve outcomes for patients. We remain committed to expanding access to selinexor across the globe with each additional ex-US approval of selinexor and look forward to working closely with Antengene to bring XPOVIO to patients in China."

About XPOVIO (selinexor)

XPOVIO is a first-in-class, oral Selective Inhibitor of Nuclear Export (SINE) compound. XPOVIO functions by selectively binding to and inhibiting the nuclear export protein exportin 1 (XPO1, also called CRM1). XPOVIO blocks the nuclear export of tumor suppressor, growth regulatory and anti-inflammatory proteins, leading to accumulation of these proteins in the nucleus and enhancing their anti-cancer activity in the cell. The forced nuclear retention of these proteins can counteract a multitude of the oncogenic pathways that, unchecked, allow cancer cells with severe DNA damage to continue to grow and divide in an unrestrained fashion. Karyopharm received accelerated U.S. Food and Drug Administration (FDA) approval of XPOVIO in July 2019 in combination with dexamethasone for the treatment of adult patients with relapsed refractory multiple myeloma (RRMM) who have received at least four prior therapies and whose disease is refractory to at least two proteasome inhibitors, at least two immunomodulatory agents, and an anti-CD38 monoclonal antibody. NEXPOVIO (selinexor) has also been granted conditional marketing authorization for adult patients with heavily pretreated multiple myeloma by the European Commission. Karyopharm’s supplemental New Drug Application (sNDA) requesting an expansion of its indication to include the treatment for patients with multiple myeloma after at least one prior therapy was approved by the FDA on December 18, 2020. In June 2020, Karyopharm received accelerated FDA approval of XPOVIO for its second indication in adult patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL), not otherwise specified, including DLBCL arising from follicular lymphoma, after at least 2 lines of systemic therapy. Selinexor is also being evaluated in several other mid-and later-phase clinical trials across multiple cancer indications, including as a potential backbone therapy in combination with approved myeloma therapies (STOMP) and in endometrial cancer (SIENDO), among others. Additional Phase 1, Phase 2 and Phase 3 studies are ongoing or currently planned, including multiple studies in combination with approved therapies in a variety of tumor types to further inform Karyopharm’s clinical development priorities for selinexor. Additional clinical trial information for selinexor is available at www.clinicaltrials.gov.

For more information about Karyopharm’s products or clinical trials, please contact the Medical Information department at:

Tel: +1 (888) 209-9326
Email: [email protected]

XPOVIO (selinexor) is a prescription medicine approved:

In combination with bortezomib and dexamethasone for the treatment of adult patients with multiple myeloma who have received at least one prior therapy (XVd).
In combination with dexamethasone for the treatment of adult patients with relapsed or refractory multiple myeloma who have received at least four prior therapies and whose disease is refractory to at least two proteasome inhibitors, at least two immunomodulatory agents, and an anti–CD38 monoclonal antibody (Xd).
For the treatment of adult patients with relapsed or refractory diffuse large B–cell lymphoma (DLBCL), not otherwise specified, including DLBCL arising from follicular lymphoma, after at least 2 lines of systemic therapy. This indication is approved under accelerated approval based on response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trial(s).
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.

On December 17, 2021, Karyopharm Therapeutics Inc. (the "Company") reported that it entered into a License Agreement (the "Agreement") with Berlin-Chemie AG, an affiliate of the Menarini Group ("Menarini"), pursuant to which the Company granted Menarini a non-exclusive license to develop, and an exclusive license to commercialize, products containing selinexor, the Company’s lead Selective Inhibitor of Nuclear Export ("SINE") compound (the "Product"), for all human oncology indications in the European Economic Area, United Kingdom, Switzerland, Armenia, Azerbaijan, Belarus, Kazakhstan, Kyrgyzstan, Moldova, Russia, Tajikistan, Turkmenistan, Uzbekistan, Ukraine, Turkey, Mexico, all Central America countries and all South America countries (collectively, the "Territory") (Filing, 8-K, Karyopharm, DEC 17, 2021, View Source [SID1234597532]). In addition, the Company granted to Menarini a non-exclusive license to package and label the Product in or outside of the Territory for all human oncology indications solely to enable Menarini to commercialize the Product within the Territory.

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Under the terms of the Agreement, the Company will use commercially reasonable efforts to develop the Product, transfer any marketing approval or authorization with respect to the Product in the Territory to Menarini and to complete any post-marketing approval or authorization studies required by a regulatory authority as a condition of maintaining the approval in any country in the Territory (the "Post-Registration Studies"). Menarini is obligated to use commercially reasonable efforts to apply for and obtain marketing approval or authorization of the Product, and to obtain price or reimbursement approval for the Product after approval of the relevant marketing approval or authorization, in each country of the Territory in each indication for which the Company has conducted a registrational clinical trial. Menarini is also obligated to use commercially reasonable efforts at its sole cost and expense to launch and commercialize the Product in each country of the Territory in each indication for which the Company has conducted a registrational clinical trial.

The Company will receive an upfront cash payment of $75.0 million in 2021, which we believe will extend the Company’s cash runway to early 2024. The Company is also entitled to receive up to $202.5 million in milestone payments from Menarini if certain development and sales performance milestones are achieved. The Company is further eligible to receive tiered royalties ranging from the mid-teens to mid-twenties based on future net sales of the Product in the Territory. The payments owed by Menarini to the Company are subject to reduction in specified circumstances. Menarini will reimburse the Company for 25% of all documented expenses incurred by the Company for the global development of the Product during 2022 through 2025, provided that such reimbursements shall not exceed $15.0 million per calendar year.

Menarini will purchase Product from the Company in accordance with a supply agreement to be entered into by the Company and Menarini (the "Supply Agreement"). The Company will supply all required quantities of selinexor and Product for the Territory as set forth in the Supply Agreement.

The development and commercialization of the Product for all human oncology indications in the Territory as contemplated by the Agreement will be subject to oversight by a joint steering committee composed of employees of the Company and Menarini, with the Company having final decision-making authority with regard to the development of the Product, as well as certain other technical, scientific and clinical operations matters, and Menarini having final decision-making authority with regard to the commercialization of the Product. Each party has also agreed to indemnify the other party from certain liabilities specified in the Agreement.

The Agreement will continue in effect on a country-by-country basis until the last to occur among: (i) the fifteenth anniversary of the first commercial sale of the Product in the applicable country, (ii) the expiration of the last-to-expire of the licensed patent rights in the applicable country or (iii) the expiration of any regulatory exclusivity protection covering the Product in such country. However, the Agreement may be terminated earlier by either party for (i) an uncured material breach of the Agreement by the other party (A) on a country-by-country basis with respect to the country to which the breach

relates if the breach is specific to such country and does not affect the Agreement as a whole or (B) in its entirety if the breach affects the Agreement as a whole, or (ii) in the event of the insolvency or bankruptcy of the other party. The Company may terminate the Agreement for certain patent challenges by Menarini.

The Company expects to file the Agreement as an exhibit to its Annual Report on Form 10-K for the year ended December 31, 2021. The foregoing is a description of certain terms

On December 17, 2021 Kineta, Inc., a clinical stage biotechnology company focused on the development of novel immunotherapies in oncology, reported the presentation of new preclinical data on the company’s anti-CD27 agonist monoclonal antibody program at the virtual European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Immuno-Oncology Congress 2021, that took place December 8-11, 2021 (Press release, Kineta, DEC 17, 2021, View Source;utm_medium=rss&utm_campaign=kineta-presented-new-preclinical-data-on-its-anti-cd27-agonist-antibody-program-at-the-esmo-immuno-oncology-congress-2021 [SID1234597371]). Thierry Guillaudeux, PhD, Senior Vice President Immuno-oncology at Kineta, presented a poster revealing compelling in vitro data on the T cell activation and cytokine induction of Kineta’s lead anti-CD27 agonist antibodies. Additionally, Dr. Guillaudeux presented new in vivo data demonstrating strong anti-tumor efficacy as a monotherapy in an MB49 tumor model.

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"We are excited to see the robust preclinical data of our anti-CD27 agonist antibodies that was presented at ESMO (Free ESMO Whitepaper)" said Thierry Guillaudeux, PhD, Senior Vice President Immuno-oncology at Kineta. "These data demonstrate the potential of our future lead anti-CD27 agonist antibodies as a monotherapy. Additionally, we believe there are combinations with other immunotherapies that can provide strong synergistic efficacy and improve outcomes for patients with cancer."

Key results from the ESMO (Free ESMO Whitepaper) poster presentation:

Evaluated 15 leads out of 147 fully human anti-CD27 monoclonal antibodies with unique sequences
Human T cell activation assay showed strong increased in proliferation and cytokine secretion for 3 mAbs
Surrogate in vivo model with anti-mouse CD27 agonist showed significant anti-tumor response
huCD27 transgenic mice will serve as our model for further in vivo studies to select our lead anti-CD27 agonist antibody

Presentation Details:

Title: Novel fully human agonist antibodies against the T-cell costimulatory receptor CD27 shape adaptive anti-tumor immunity
Date Presented: December 8-11, 2021
Presenter: Thierry Guillaudeux, PhD
Poster: Click on the link below to view the poster:

CD27 Publications – Poster Presentation at ESMO (Free ESMO Whitepaper) 2021

Anti-CD27 mAb program: Kineta has developed a diverse set of anti-CD27 agonist antibodies. They are fully human monoclonal antibodies (mAbs) that demonstrate low nanomolar (nM) binding affinity to CD27 in humans. In preclinical studies, Kineta’s selected lead anti-CD27 agonist mAbs induce T cell proliferation and secretion of cytokines involved in T cell priming and recruitment, demonstrating the ability to potentiate new anti-tumor responses. Kineta is in the final stage of lead selection and plans to nominate a clinical candidate in Q1-Q2 2022.

On December 17, 2020. PledPharma AB (publ) (ticker: PLED) reported that the company has formally changed its name to Egetis Therapeutics AB (publ) (ticker: EGTX). The decision was made at the Annual General Meeting on December 11, 2020. The name change is a result of the acquisition of Rare Thyroid Therapeutics AB (RTT) and the company’s new strategic focus on the development of orphan drugs for rare diseases (Press release, Egetis Therapeutics, DEC 17, 2021, View Source [SID1234591214]).

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PledPharma announced the acquisition of RTT in early October 2020. In order to illuminate the new strategic direction and focus on orphan drugs in late clinical development, it was also announced that the new company will be named Egetis Therapeutics. The name alludes to the company’s focus on rare diseases where there are great medical needs and no or few adequate forms of treatment today. Egetis is Latin and means "You need/lack". The decision on the name change was formally made at the Annual General Meeting on December 11, 2020.

"With Egetis Therapeutics, we get a name that reflects our focus on rare diseases where there are great medical needs. Our ambition is to build a specialized company for the development of orphan drugs, and with the acquisition of RTT, we already have two orphan drugs in late clinical development with Emcitate and Aladote from the start. The ambition is to build a portfolio of orphan drugs that can potentially improve and change the lives of many patients around the world", said Egetis Therapeutics CEO Nicklas Westerholm.

The company has also launched a new website where the new focus and projects are presented in more detail. For more information, visit www.egetis.com. To contact Egetis Therapeutics, please use the email address [email protected].