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.

On December 8, 2020 Novartis reported thatn Detailed results from the Phase III ASCEMBL study demonstrate that, at 24 weeks, asciminib (ABL001) – a novel investigational treatment specifically targeting the ABL myristoyl pocket (STAMP) – nearly doubled the major molecular response (MMR) rate compared to Bosulif (bosutinib)* (25.5% vs. 13.2%, respectively ([95% CI, 2.19-22.3]; 2-sided P=0.029) in patients with Philadelphia chromosome-positive chronic myeloid leukemia in chronic phase (Ph+ CML-CP) previously treated with two or more tyrosine-kinase inhibitors (TKIs)1 (Press release, Novartis, DEC 8, 2020, View Source [SID1234572447]). These data were presented today at a late-breaking abstracts session during the 62nd American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting & Exposition (ASH) (Free ASH Whitepaper).

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"These important comparative data are impressive, and they reinforce the critical role asciminib may play, if approved, in overcoming the treatment challenges we face in later treatment lines of chronic-phase CML," said Dr. Michael J. Mauro**, Member and Myeloproliferative Neoplasms Program Leader at Memorial Sloan Kettering Cancer Center and Professor at Weill Cornell Medicine. "While the advent and expansion of TKI therapies has resulted in tremendous progress for patients living with CML over the last decades, many of our patients in later treatment lines still face inadequate response, disease progression and intolerable side effects."

Despite the significant advances in the CML treatment landscape, many patients treated with two or more TKIs experience intolerance; for example, in an analysis of studies in patients who had previously failed two TKIs, up to 55% reported intolerance to treatment8-13. In addition, resistance rates for patients in later treatment lines remain high; and in the second-line setting, at least three out of five patients are unable to achieve MMR and up to 56% of patients do not achieve complete cytogenetic response (CCyR) within two years of follow-up5,13-18. With few remaining treatment options, and no currently established standard-of-care in the third-line setting per treatment guidelines, patients who are resistant or intolerant to two or more TKIs are at a high risk of progression2-5,19-21.

In the ASCEMBL trial, 233 patients were randomized to receive asciminib 40 mg twice daily (n=157) or Bosulif 500 mg once a day (n=76)1. Data showed that, at 24 weeks, more patients achieved a CCyR in the asciminib arm (40.8%) than in the Bosulif arm (24.2%); and deep molecular response (DMR) rates were higher for patients in the asciminib arm than in the Bosulif arm – with 10.8% and 8.9% patients achieving MR4 and MR4.5 on asciminib, respectively, vs. 5.3% and 1.3% on Bosulif1.

Grade ≥3 adverse events (AEs) occurred in 50.6% and 60.5% of patients treated with asciminib and Bosulif, respectively1. Treatment discontinuation due to AEs in the asciminib arm was 5.8% compared to 21.1% for patients taking Bosulif 1. Similarly, AEs requiring dose interruption and/or dose adjustments were reported less frequently with asciminib than with Bosulif (37.8% vs. 60.5%, respectively)1. At data cutoff, more patients were still on treatment in the asciminib arm vs. the Bosulif arm (61.8% vs. 30.3%, respectively)1.

The most common grade ≥3 AEs (occurring in >10%) of patients treated with asciminib were thrombocytopenia (17.3%) and neutropenia (14.7%), while for Bosulif they were increased alanine aminotransferase (ALT) (14.5%), neutropenia (11.8%) and diarrhea (10.5%)1. On-treatment deaths on the asciminib arm occurred in two (1.3%) patients (ischemic stroke and arterial embolism); there was one (1.3%) death on Bosulif (septic shock)1. The most frequent AEs (all grades; ≥20%) were thrombocytopenia (28.8%) and neutropenia (21.8%) in the asciminib arm, compared to diarrhea (71.1%), nausea (46.1%), increased ALT (27.6%), vomiting (26.3%), rash (23.7%), increased aspartate aminotransferase (21.1%), neutropenia (21.1%) and thrombocytopenia (18.4%) in the Bosulif arm1.

"Though some patients with CML may be told they have a ‘good cancer’ because of the wonderful advances in care that have been made over the years, this doesn’t capture the full picture for everyone with the disease," said Greg Stephens, Executive Director and Founder of the US National CML Society. "The results of the ASCEMBL study are very encouraging to the CML community, and help underscore the crucial need for additional treatment options to address real challenges that patients face."

Pre-clinical data suggests that asciminib has specificity for BCR-ABL22. Additional data accepted for online publication highlight that, as an investigational STAMP inhibitor, asciminib is designed to help overcome mutations on the ATP-binding site of BCR-ABL1, which may help address resistance in later treatment lines of CML and may potentially address off-target activity22.

"Novartis has been at the forefront of CML research for years – significantly changing the prognosis for patients. We are very proud to once again advance a potentially transformative medicine, a novel STAMP inhibitor, for those who do not adequately respond or are intolerant to currently available TKIs," said John Tsai, Head Global Drug Development and Chief Medical Officer, Novartis. "There is a clear need in later lines of therapy, and based on these results, we believe asciminib may become an important new development for patients. We look forward to sharing the data with regulatory authorities and moving forward with submissions worldwide."

The US Food and Drug Administration (FDA) has granted Fast Track designation for asciminib. Submission to the US and EU health authorities is planned for the first half of 2021.

Visit View Source for the latest information from Novartis including our bold approach to reimagining care in hematology, and access to our ASH (Free ASH Whitepaper) Virtual Congress 2020 symposia and data presentations (for registered participants).

About asciminib (ABL001)
Asciminib (ABL001) is an investigational treatment specifically targeting the ABL myristoyl pocket (STAMP). As a STAMP inhibitor, asciminib may help address tyrosine-kinase inhibitor (TKI)-resistance and intolerance in later treatment lines of chronic myeloid leukemia (CML), and it is being studied in several clinical trials in hopes of helping patients across multiple treatment lines of CML23-30.

About ASCEMBL
ASCEMBL is a Phase III, multicenter, open-label, randomized study comparing the oral investigational treatment asciminib (ABL001) versus bosutinib in patients with Philadelphia chromosome-positive chronic myeloid leukemia in chronic phase (Ph+ CML-CP) previously treated with two or more tyrosine-kinase inhibitors (TKIs)1. Patients with failure or intolerance to the most recently administered TKI therapy were included in the trial1.

About Novartis Commitment to CML
Our ongoing research in Philadelphia chromosome-positive chronic myeloid leukemia (Ph+ CML) has helped transform the disease from a fatal leukemia to a chronic condition in most patients. Novartis maintains an unwavering commitment to scientific innovation and access to care for patients worldwide. As an organization committed to patients, Novartis continues to reimagine CML care by pursuing ambitious goals with courage, passion and commitment for the global CML community.

On December 8, 2020 Eli Lilly and Company (NYSE: LLY) reported that it will announce its financial guidance for 2021 on Tuesday, December 15, 2020 (Press release, Eli Lilly, DEC 8, 2020, View Source [SID1234572446]). Lilly will also conduct a conference call on that day with the investment community and media to further detail the company’s financial guidance.

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The conference call will begin at 8:30 a.m. Eastern time. Investors, media and the general public can access a live webcast of the conference call through a link that will be posted on Lilly’s website at View Source A replay will also be available on the website following the conference call.