On December 8, 2020 Turning Point Therapeutics, Inc. (NASDAQ: TPTX), a precision oncology company developing next-generation therapies that target genetic drivers of cancer, reported its lead drug candidate, repotrectinib, has been granted breakthrough therapy designation by the Food and Drug Administration (FDA) for the treatment of patients with ROS1-positive metastatic non-small cell lung cancer (NSCLC) who have not been treated with a ROS1 tyrosine kinase inhibitor (TKI-naïve) (Press release, Turning Point Therapeutics, DEC 8, 2020, View Source [SID1234572452]).

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"Breakthrough therapy designation is another milestone in our development of repotrectinib and one more step towards our goal to get this potentially important drug candidate to patients as quickly as possible," said Athena Countouriotis, M.D., president and chief executive officer. "I am incredibly proud of our Turning Point team with the achievement of our fourth regulatory designation from the FDA for repotrectinib, and pleased with how our enrollment specifically in the ROS1 TKI-naive population of the TRIDENT-1 study has progressed since we reported initial early Phase 2 data. We look forward to sharing more information on our overall study timelines early next year, and providing updated data from the TRIDENT-1 study next month."

Turning Point plans to present updated TRIDENT-1 Phase 2 study data from patients with TKI-naive ROS1-positive NSCLC during a mini-oral presentation at the World Conference on Lung Cancer on Jan. 31, 2021.

The breakthrough therapy designation for repotrectinib was supported by the initial data from TKI-naïve ROS1-positive NSCLC patients enrolled in the Phase 1 and Phase 2 portions of the TRIDENT-1 study, which is currently evaluating patients in multiple potentially registrational cohorts.

Breakthrough therapy designation is granted by the FDA to expedite the development and regulatory review of an investigational medicine that is intended to treat a serious or life-threatening condition. The criteria for breakthrough therapy designation require preliminary clinical evidence that demonstrates the drug may have substantial improvement on at least one clinically significant endpoint over available therapy. Repotrectinib was previously granted three Fast Track designations by the FDA, in ROS1-positive NSCLC patients who are TKI naïve, ROS1-positive NSCLC patients who have been previously treated with one prior platinum chemotherapy and one prior ROS1 TKI, and NTRK-positive patients with advanced solid tumors who have progressed following treatment with at least one prior line of chemotherapy and one or two prior TRK TKIs.

On December 8, 2020 Harpoon Therapeutics, Inc. (NASDAQ: HARP), a clinical-stage immunotherapy company developing a novel class of T cell engagers, reported a pipeline update and reported a confirmed partial response based on RECIST v1.1 criteria for its most advanced program, HPN424 for the treatment of metastatic castration-resistant prostate cancer (mCRPC) (Press release, Harpoon Therapeutics, DEC 8, 2020, View Source [SID1234572451]). As of December 1, 2020, in the 160ng/kg cohort, which is the highest fixed dose tested to date, 7 patients have been enrolled and one patient has achieved a confirmed partial response. In addition, 3 patients enrolled in this cohort had serum PSA reductions, including one with a reduction of 50% (PSA50). Dose escalation continues in this trial, in the Phase 1/2a clinical trials for HPN536 as a treatment for ovarian cancer and other mesothelin-expressing solid tumors and in the HPN217 Phase 1/2 clinical trial for multiple myeloma. Step dosing is being utilized in all programs to accelerate testing of higher doses. Dosing of the first patient in the Phase 1/2 trial for Harpoon’s fourth TriTAC development program, HPN328, in small cell lung cancer and other DLL3-associated tumors is expected to occur by the end of the year.

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"We are pleased to provide a trial update to our shareholders today, as well as outline our expectations for 2021. We have made significant progress in all of our clinical development programs in 2020," stated Gerald McMahon, Ph.D., President and CEO of Harpoon Therapeutics. "We are excited to report our first confirmed partial response in the continuing dose escalation trial for HPN424, especially in a heavily pretreated patient population with advanced metastatic disease. We are also excited by the potential for multiple data releases in 2021 on all four of our programs, which we believe represent meaningful milestones for our company."

"We are pleased to report the activity we are seeing with HPN424 in late-stage prostate cancer patients in our highest fixed dose cohort tested to date," said Natalie Sacks, M.D., Chief Medical Officer of Harpoon. "We are implementing step dosing in all of our programs, which allows rapid escalation to higher doses. We look forward to sharing data from these higher-dose cohorts in 2021."

Clinical Program Updates
(All data as of December 1, 2020)

Dose escalation continues in Phase 1/2a trial for HPN424 in the treatment of mCRPC. As of the December 1, 2020 data cutoff date, 69 patients have been dosed across 14 cohorts at fixed doses of 1.3 to 160ng/kg and in step dosing cohorts up to 300ng/kg administered as a weekly intravenous infusion. Enrolled patients had a median of 6 prior systemic therapies, and 76% of patients had prior chemotherapy in the metastatic castration-resistant setting. Ten of 44 patients (23%) with treatment start dates at least 6 months ago remained on study treatment for more than 24 weeks.

At the highest fixed dose tested to date, 160ng/kg, one patient out of 7 has experienced a confirmed partial response with tumor lesion reduction of 43%, and 3 of 7 patients have had serum PSA declines from baseline, including one patient with a PSA reduction greater than 50%.

HPN424 was generally well tolerated and cytokine-related adverse events have been manageable. Reported Grade 3 or higher adverse events have included cytokine release syndrome (CRS) (10%), ALT increase (11%) and AST increase (11%). CRS events and transaminitis have been transient and have not resulted in treatment discontinuation. Dose-limiting toxicities (DLTs) have been observed and have not limited escalation. A maximum tolerated dose (MTD) has not been identified. Presentation of Phase 1 data and initiation of an expansion cohort is planned for the first half of 2021. Interim data from this expansion cohort is anticipated by the end of 2021.

HPN536 (mesothelin TriTAC) Phase 1/2a clinical trial continues escalation. Dosing has occurred across 9 fixed-dose cohorts of 6 to 280ng/kg and 1 step dose cohort up to 600ng/kg. Tumor types treated include late-stage ovarian and pancreatic cancers and peritoneal mesothelioma. Enrolled patients had a median of four prior systemic therapies, and 66% of patients had progressive disease as best response to their most recent prior therapy. Pharmacokinetic analysis shows median half-life of more than 70 hours. Among the relapsed/refractory ovarian cancer patients with at least one post-baseline scan, 8 of 12 (67%) patients showed stability of target lesions.

HPN536 appears to be well tolerated. One CRS grade 3 occurred in the absence of dexamethasone premedication treatment. The CRS resolved, and the patient continued on study with dexamethasone premedication. As of December 1, 2020, no DLTs have been observed. Initiation of an expansion cohort is anticipated by the second half of 2021, with a presentation of Phase 1 data by year-end 2021.

Dose escalation for HPN217 (BCMA TriTAC) Phase 1/2 clinical trial progressing rapidly. Relapsed/refractory multiple myeloma patients have been treated across 6 single-patient fixed dose cohorts of 5 to 810µg, reflecting a more than 100-fold increase in dose in 8 months. HPN217 has been well-tolerated, and no DLTs have been observed as of the December 1, 2020 cutoff date. A presentation of interim data is anticipated in 2021, with initiation of a dose expansion cohort in the second half of 2021.

First patient dosing anticipated for HPN328 (DLL3 TriTAC) by the end of 2020. The first site is open and recruiting for the dose escalation portion of this Phase 1/2 clinical trial. In the first cohort, the patients will receive a flat dose of 15µg of HPN328 administered once weekly by intravenous infusion. Eligible patients include small cell lung cancer patients who have relapsed after platinum chemotherapy and patients with other tumors associated with DLL3 expression. Presentation of initial data is planned for the second half of 2021.

Webcast and Conference Call

Harpoon’s management will host a webcast and conference call at 8 a.m. ET / 5 a.m. PT on December 8, 2020. The live call may be accessed by dialing (866) 951-6894 for domestic callers and (409) 216-0624 for international callers with conference ID code number 1388395. A webcast of the live call will be available online in the investor relations section of the Harpoon website at www.harpoontx.com. A replay of the webcast will be available shortly after the event and can be accessed at the same weblink.

On December 8, 2020 Actinium Pharmaceuticals, Inc. (NYSE AMERICAN: ATNM) ("Actinium" or the "Company") reported that first-in-human data from the first dose cohort of the Phase 1 portion of the Actimab-A venetoclax Phase 1/2 combination trial in patients with relapsed or refractory Acute Myeloid Leukemia (AML) were presented at the 62nd American Society of Hematology (ASH) (Free ASH Whitepaper) annual meeting (Press release, Actinium Pharmaceuticals, DEC 8, 2020, View Source [SID1234572450]). The poster presentation highlighted results from the first three patients treated with the initial subtherapeutic dose level of 0.5 μCi/kg of Actimab-A and venetoclax.

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The enrolled patients had a median of 2 prior therapies (range 2-3) and a median bone marrow blast percentage of 30% (range 20 – >60). All 3 patients had poor risk disease with adverse cytogenetics, and each patient had an additional high-risk marker (FLT3-ITD+, antecedent JAK2+ myelofibrosis, or TP53 mutation). One patient who had multiple genetic mutations including IDH2, RUNX1, TP53 and others, achieved a complete remission with incomplete blood count recovery (CRi) after the first cycle of Actimab-A and venetoclax. Next generation sequencing at the end of the first cycle showed that patient was negative for the known IDH2 and RUNX1 mutations. This patient has continued treatment receiving the second cycle and their bone marrow remains normocellular with no excess blasts. In addition, another patient achieved a partial response after one cycle of Actimab-A and venetoclax. There were no Actimab-A related dose limiting toxicities or nonhematologic Grade 3 or greater related AEs reported in the first cohort. The trial has advanced to the second dose cohort of 1.0 μCi/kg of Actimab-A and venetoclax with patient enrollment ongoing.

Sandesh Seth, Actinium’s Chairman and Chief Executive Officer, commented, "This ASH (Free ASH Whitepaper) meeting, we are excited to highlight the promising data emerging from both our combination trials with Actimab-A in the R/R AML setting, namely the Actimab-A venetoclax and Actimab-A CLAG-M trials. Particularly compelling is the complete response reported in a patient with complex mutations like TP53 with Actimab-A and venetoclax and the high MRD negativity rate with Actimab-A and CLAG-M. The results clearly demonstrate that a superior clinical effect without adding meaningful toxicity is achievable using Ac-225 ARC’s to precisely deliver powerful internal radiation and elicit a potentiating and synergistic treatment effect with chemotherapy and targeted agents. With this clinical validation in hand, we look forward to expanding our ARC combinations with other therapeutic modalities in AML and into additional indications to further establish our leadership position in the field by leveraging our enhanced R&D capabilities including new research facilities and key hires."

Dr. Mark Berger, Actinium’s Chief Medical Officer, said, "We were thrilled to report a complete response in the Actimab-A venetoclax combination trial, in addition to the partial response previously highlighted in the abstract. Both responses occurred after just one cycle of a subtherapeutic dose of Actimab-A. These initial results, the one complete response and safety profile to date, support the potential mechanistic synergy of Actimab-A with venetoclax. As a single agent, venetoclax has produced low response rates of 19% in patients with R/R AML1 so we are pleased with the results seen in our first dose cohort. In addition, the clinical data from Actimab-A and Iomab-B presented at this year’s ASH (Free ASH Whitepaper) demonstrates our strong commitment to addressing the unmet needs of patients with R/R AML with our ARCs as best in class therapeutics, bridge to transplant and targeted conditioning for potentially curable bone marrow transplant. With this in mind, we look forward to guidance on Iomab-B expected from the ad-hoc DMC meeting before year-end."

This Phase 1/2 trial is a multicenter, open label trial of Actimab-A (lintuzumab-Ac225) added to venetoclax for patients with CD33 positive R/R AML. A Phase 2 trial studying Actimab-A as a single agent produced a 69% overall response rate in older unfit patients with newly diagnosed AML. In a poster presentation at the American Association of Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2019, Actimab-A was shown to be synergistic with venetoclax in venetoclax resistant cell lines, by depleting MCL-1, a protein shown to mediate resistance to venetoclax. Further, the induction of direct AML cell death via double-stranded DNA breaks by Actimab-A provides a second mechanism for enhancing synergistic potency with venetoclax. Venetoclax is a B-Cell Lymphoma 2 (BCL-2) inhibitor that is jointly developed and marketed by AbbVie and Genentech and is approved for patients with AML, Chronic Lymphocytic Leukemia (CLL), and Small Lymphocytic Leukemia (SLL). Despite its approval in AML, venetoclax has produced low response rates of 19% as a single agent in R/R AML.1 This is due in part to the type of AML, risk factors, and cytogenetics of this patient population. The Phase 2 trial results, together with a synergistic mechanism of action with venetoclax demonstrated in pre-clinical studies, are driving this combination trial with an initial focus on the high unmet needs of R/R patients including those who have relapsed or do not respond to treatment with venetoclax based regimens.

1 Aldosset al. Efficacy of the combination of venetoclax and hypomethylating agents in relapsed/refractory acute myeloid leukemia. Haematologica2018.1888094.

About Actinium’s CD33 Program

Actinium’s CD33 program is evaluating the clinical utility of Actimab-A, an ARC comprised of the anti-CD33 mAb lintuzumab linked to the potent alpha-emitting radioisotope Actinium-225 or Ac-225. CD33 is expressed in the majority of patients with AML and myelodysplastic syndrome, or MDS, as well as patients with multiple myeloma. The CD33 development program is driven by data from over one hundred treated patients, including a Phase 1/2 trial where Actimab-A produced a remission rate as high as 69% as a single agent. This clinical data is shaping a two-pronged approach for the CD33 program, where at low doses the Company is exploring its use for therapeutic purposes in combination with other modalities and at high doses for use for targeted conditioning prior to bone marrow transplant. Actinium currently has multiple clinical trials ongoing including the Phase 1 Actimab-A CLAG-M and Phase 1/2 Actimab-A venetoclax combination trials and is exploring additional CD33 ARC combinations with other therapeutic modalities such as chemotherapy, targeted agents or immunotherapy.

On December 8, 2020 HOOKIPA Pharma Inc. (Nasdaq: HOOK), a company developing a new class of immunotherapeutics based on its proprietary arenavirus platform, reported the pricing of an underwritten public offering of 3,400,000 shares of its common stock and 2,978 shares of its Series A convertible preferred stock (the "Offering") (Press release, Hookipa Pharma, DEC 8, 2020, View Source [SID1234572449]). The public offering price of each share of common stock is $11.75 and the public offering price of each share of Series A preferred stock is $11,750 (each share of Series A preferred stock is convertible into 1,000 shares of common stock). HOOKIPA has granted the underwriters a 30-day option to purchase up to an additional 510,000 shares of its common stock at the public offering price of the common stock, less underwriting discounts and commissions. The gross proceeds to HOOKIPA from this offering are expected to be approximately $75 million, before deducting underwriting discounts and commissions and other offering expenses and excluding any exercise of the underwriters’ option to purchase additional shares. All of the securities in the Offering are to be sold by HOOKIPA. The offering is expected to close on December 11, 2020, subject to customary closing conditions.

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Morgan Stanley and SVB Leerink are acting as joint book-running managers of the Offering. RBC Capital Markets is acting as lead manager.

The securities described above are being offered by HOOKIPA pursuant to a shelf registration statement on Form S-3 (No. 333-238311), including a base prospectus filed with the Securities and Exchange Commission (the "SEC"), which was declared effective on May 27, 2020. A preliminary prospectus supplement has been filed with the SEC. A final prospectus supplement and accompanying prospectus relating to the Offering will be filed with the SEC and will be available on the SEC’s website located at www.sec.gov. Copies of the final prospectus supplement and the accompanying prospectus may also be obtained, when available, from: Morgan Stanley & Co. LLC, Attention: Prospectus Department, 180 Varick Street, 2nd Floor, New York, New York 10014; or email: [email protected] or SVB Leerink LLC, Attention: Syndicate Department, One Federal Street, 37th Floor, Boston, Massachusetts 02110; by telephone at (800) 808-7525, ext. 6132; or email: [email protected].

This press release shall not constitute an offer to sell or the 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.

On December 8, 2020 Kura Oncology, Inc. (Nasdaq: KURA), a clinical-stage biopharmaceutical company committed to realizing the promise of precision medicines for the treatment of cancer, reported the pricing of an underwritten public offering of 8,110,000 shares of its common stock at a price to the public of $37.00 per share (Press release, Kura Oncology, DEC 8, 2020, View Source [SID1234572448]). The gross proceeds to Kura from the offering, before deducting underwriting discounts and commissions and other offering expenses payable by Kura, are expected to be approximately $300 million. In addition, Kura has granted the underwriters a 30-day option to purchase up to an additional 1,216,500 shares of common stock. The offering is expected to close on or about December 11, 2020, subject to customary closing conditions.

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SVB Leerink, Credit Suisse, Barclays and Stifel are acting as joint bookrunning managers in the offering. Wedbush PacGrow, JMP Securities and H.C. Wainwright & Co. are acting as co-managers for the offering.

The securities described above are being offered by Kura pursuant to a shelf registration statement on Form S-3, including a base prospectus, that was previously filed by Kura and became effective by rule of the Securities and Exchange Commission (the "SEC") on December 7, 2020. A final prospectus supplement and accompanying prospectus relating to the offering will be filed with the SEC and will be available for free on the SEC’s website located at View Source Copies of the final prospectus supplement and the accompanying prospectus relating to the offering, when available, may be obtained from: SVB Leerink LLC, Attention: Syndicate Department, One Federal Street, 37th Floor, Boston, MA 02110, by telephone at (800) 808-7525, ext. 6132, or by email at [email protected]; Credit Suisse Securities (USA) LLC, Attention: Prospectus Department, 6933 Louis Stephens Drive, Morrisville, NC 27560, by telephone at (800) 221-1037, or by email at [email protected]; Barclays Capital Inc., c/o Broadridge Financial Solutions, 1155 Long Island Avenue, Edgewood, NY 11717, by email at [email protected] or by telephone at (888) 603-5847; or Stifel, Nicolaus & Company, Incorporated, Attention: Syndicate, One Montgomery Street, Suite 3700, San Francisco, CA 94104, by email at [email protected] or by telephone at (415) 364-2720.

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