On June 25, 2019 Mirati Therapeutics, Inc. (Nasdaq: MRTX) reported the pricing of an underwritten public offering of 2,100,000 shares of its common stock at a price to the public of $97.00 per share (Press release, Mirati, JUN 25, 2019, View Source [SID1234537250]). The aggregate gross proceeds from this offering are expected to be approximately $203.7 million, before deducting underwriting discounts and commissions and estimated offering expenses payable by Mirati. The offering is expected to close on or about June 27, 2019, subject to customary closing conditions. Mirati has also granted the underwriters a 30-day option to purchase up to an additional 315,000 shares of common stock in connection with the public offering. All of the shares are being sold by Mirati.

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Mirati expects to use the net proceeds from this offering for general corporate purposes, including expenses related to the clinical development of sitravatinib and MRTX849, the preclinical development of its KRAS G12D inhibitor and the development of other preclinical programs, and for working capital.

Cowen, Credit Suisse and Barclays are acting as joint book-running managers in the offering. Guggenheim Securities and Oppenheimer & Co. are acting as co-lead managers and H.C. Wainwright & Co. is acting as co-manager in the offering.

The shares of common stock described above are being offered by Mirati pursuant to a shelf registration statement filed by Mirati with the Securities and Exchange Commission ("SEC") that became automatically effective upon filing. A preliminary prospectus supplement and accompanying prospectus relating to the offering were filed with the SEC and are available 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 Cowen and Company, LLC, c/o Broadridge Financial Solutions, 1155 Long Island Avenue, Edgewood, NY,11717, Attn: Prospectus Department, or by telephone: (631) 592-5973, or by emailing [email protected]; from Credit Suisse Securities (USA) LLC, Attention: Prospectus Department, Eleven Madison Avenue, 3rd floor, New York, NY 10010, or by telephone: (800) 221-1037, or by emailing [email protected]; or from Barclays Capital Inc., c/o Broadridge Financial Solutions, 1155 Long Island Avenue, Edgewood, NY 11717, or by calling (888) 603-5847, or by email at [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 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 June 25, 2019 Actinium Pharmaceuticals, Inc. (NYSE AMERICAN: ATNM) ("Actinium") reported at SNMMI or the 2019 Society of Nuclear Medicine and Molecular Imaging Annual Meeting that effective lymphodepletion with the radioisotope Lu-177 or lutetium-177 was achieved with its ACT or Adoptive Cell Therapy program for achieving safe, effective and transient lymphodepletion prior to the administration of CAR-T and other adoptive cell therapies (Press release, Actinium Pharmaceuticals, JUN 25, 2019, View Source [SID1234537249]). The ARC’s or Antibody Radiation-Conjugates used in the ACT program combines a CD45 targeting antibody with the cell killing power of radioisotopes.

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Lymphodepletion is an important step prior to CAR-T and adoptive cell therapies that facilitates infused cells to engraft, expand and persist. Currently, chemotherapy such as Flu/Cy or Fludarabine and Cyclophosphamide are used in standard practice for lymphodepletion. Patients receiving CAR-T and other adoptive cell therapies are often heavily pre-treated and their cancer is refractory or resistant to chemotherapy. Actinium is developing its ACT program to be a potential replacement of non-specific, chemotherapy-based lymphodepletion.

In vivo animal studies demonstrated that a Lu-177 labeled CD45 ARC transiently depleted CD45 positive immune cells while sparing platelets, red blood cells and bone marrow cells. A dose response was observed with 40µCi Lu-177 having a greater lymphodepletion effect on immune cells — including B-cells, CD8 and CD4 T-cells, NK cells, myeloid derived suppressor cells and regulatory T-cells — than 20µCi Lu-177. In tumor bearing mice, the Lu-177 labeled CD45 ARC was given prior to adoptive cell therapy, which demonstrated enhanced tumor control when compared to mice that were untreated and those that only received adoptive cell therapy with no lymphodepletion (Click here for the SNMMI poster).

Dr. Dale Ludwig, Actinium’s Chief Scientific Officer, said, "I am truly excited by these additional results from our ACT program that we have presented at SNMMI evaluating lutetium-177 for targeted lymphodepletion. The data generated exceeded my expectations and support the continued development of a Lu-177 CD45 ARC as part of our ACT program. As we work to establish collaborations and partnerships while advancing the ACT program into clinical trials, the expansion to multiple warheads will give us flexibility and utility that I trust will be well received. I look forward to highlighting our continued efforts in this area at future medical conferences and industry meetings."

The antigen CD45 is uniquely expressed on leukemia, lymphoma and immune cells making it an ideal target for targeted condition prior to BMT or Bone Marrow Transplant, CAR-T and adoptive cell therapies. Actinium’s Iomab-B and ACT programs utilize the anti-CD45 antibody apamistamab. Apamistamab has been studied in over 300 patients in 13 clinical trials, including the ongoing pivotal Phase 3 SIERRA trial, across multiple hematologic indications including acute myeloid leukemia, myelodysplastic syndrome, acute lymphoblastic leukemia, lymphomas and multiple myeloma. The ACT program utilizes a lower dose of the radioisotope I-131 or Iodine-131 than Iomab-B and can now also utilize Lu-177.

Actinium presented initial feasibility data for its ACT program at the Transplantation and Cellular Therapies Meeting in February 2019. The data demonstrated that a CD45 targeting antibody labeled with I-131 effectively depleted greater than 90% of lymphocytes in preclinical animal models (Click here for poster).

Sandesh Seth, Actinium’s Chairman and CEO, said, "I am excited to add the lutetium-177 warhead to our targeted conditioning armamentarium and expand our ACT program beyond iodine-131. Our targeted conditioning ARC’s are demonstrating promising results across our portfolio, including in our pivotal Phase 3 Iomab-B program for BMT and the ACT program for lymphodepletion for CAR-T and adoptive cell therapies. These therapies have the potential to significantly benefit patients and, in some instances, lead to long lasting remissions or even cures. We are confident that our targeted conditioning ARC’s can increase the number of patients that can receive these important therapies and improve patient outcomes. Recognizing the growth potential of this field we are committed to continuing to drive innovation across our ARC portfolio and further strengthening our leadership position in targeted conditioning."

On June 25, 2019 Arvinas, Inc. (Nasdaq: ARVN), a biotechnology company creating a new class of drugs based on targeted protein degradation, reported that the U.S. Food and Drug Administration (FDA) has cleared the company’s Investigational New Drug application (IND) for ARV-471, an oral estrogen receptor (ER) PROTAC protein degrader, designed to selectively target ER for the treatment of patients with locally advanced or metastatic ER positive / HER2 negative breast cancer (Press release, Arvinas, JUN 25, 2019, View Source [SID1234537248]). Arvinas expects to initiate a Phase 1 clinical trial for ARV-471 in the third quarter of 2019.

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"ARV-471 is our second program in six months to receive IND clearance, and we are pleased to be advancing it into the clinic and progressing Arvinas’ portfolio of PROTAC protein degraders for the treatment of patients with cancer and other life-threatening diseases," said John Houston, Ph.D., President and CEO of Arvinas. "We hope the activity ARV-471 demonstrated preclinically will translate into a new, beneficial treatment for patients with locally advanced or metastatic ER positive/HER2 negative breast cancer."

In the United States, breast cancer is the second most common cancer and the second leading cause of cancer death in women. The American Cancer Society estimates that in 2019, there will be approximately 268,000 women diagnosed with invasive breast cancer in the United States. Metastatic breast cancer accounts for approximately 6% of newly diagnosed cases. Approximately 80% of newly diagnosed breast cancers are ER positive, with many patients developing resistance to current treatment options over time.

ARV-471 is a PROTAC protein degrader specifically designed to target and degrade ER. The Phase 1 trial will assess the safety, tolerability, and pharmacokinetics of ARV-471, and will also include measures of anti-tumor activity and pharmacodynamic readouts as secondary endpoints.

In preclinical studies, ARV-471 demonstrated near-complete ER degradation in tumor cells, induced robust tumor shrinkage when dosed as a single agent in multiple ER-driven xenograft models, and showed superior anti-tumor activity as a single agent and in combination with a CDK4/6 inhibitor when compared to a standard of care agent, fulvestrant, dosed as single agent or in combination with a CDK4/6 inhibitor. Arvinas believes the differentiated pharmacology of ARV-471, including its iterative degradation activity, has the potential to translate into meaningful clinical benefit for patients.

On June 25, 2019 Taiwan Liposome Company, Ltd. ("TLC") (Nasdaq: TLC, TWO: 4152), a clinical-stage specialty pharmaceutical company dedicated to the development and commercialization of novel nanomedicines designed to target areas of unmet medical need in osteoarthritis, pain management, ophthalmology and oncology, reported the signing of a development and license agreement with Birdie Biopharmaceuticals Inc. ("Birdie"), a wholly owned subsidiary of Seven and Eight Biopharmaceuticals Corp (Press release, Taiwan Liposome Company, JUN 25, 2019, View Source [SID1234537247]). Birdie and Seven and Eight Biopharmaceuticals are clinical stage biotech companies focused on the development of immunotherapy to treat cancer.

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Under the agreement, Birdie will engage TLC in the development and manufacturing of a liposomal formulated dual agonist product against toll-like receptors 7 and 8 (TLR7/8) utilizing TLC’s NanoX technology. Birdie will be responsible for the product’s preclinical and clinical development, regulatory filing and commercialization. TLC will be responsible for the formulation development and manufacturing. TLC will receive an upfront payment and is eligible to receive up to US$49 million in potential milestone payments. In addition, TLC is also eligible to royalties based on the net sales.

"This agreement leverages our expertise and gives further validation to our technology platform’s capability to expand into other areas such as immunotherapy for the treatment of cancer," commented TLC President George Yeh. "Our NanoX liposome technology has distinct advantages of achieving desirable pharmacokinetic profiles and preferential distribution to tumor tissues. We are delighted to partner with Birdie and working together on this collaboration to bring a potential new innovative therapy to cancer patients."

"TLR7/8 are amongst the most promising targets for immuno-oncology and our dual agonists have demonstrated the ability to stimulate specific types of innate immune response, generating enhanced anti-tumor immunity," said, Walter Lau, Ph.D., Chief Executive Officer of Birdie and Seven and Eight Biopharmaceuticals. "Following our recent announced collaboration with a major pharma partner on combination trials with established checkpoint inhibitors, we are excited to be working with TLC to develop a potential best-in-class next generation product. We believe that the robust, scalable and replicable manufacturing process of TLC’s NanoX technology formulates a sustainable competitive advantage and the potential to commercialize worldwide."

On June 25, 2019 Dune Medical Devices reported that it has reached another milestone in their MarginProbe Post Approval Study (PAS) as Johns Hopkins Hospital and Moffitt Cancer Center complete their patient enrollments for the trial (Press release, Dune Medical Devices, JUN 25, 2019, http://www.dunemedical.com/prestigious-cancer-centers-johns-hopkins-and-moffitt-complete-patient-enrollment-in-post-approval-study-for-marginprobe-transforming-the-standard-of-care-for-breast-cancer-patients/ [SID1234537245]). This PAS, required by the FDA, seeks to substantiate the vast body of data produced since MarginProbe’s original approval, demonstrating its effectiveness at intraoperatively identifying positive margins and subsequent effects on reducing re-excision rates while maintaining cosmetic outcomes after surgery.

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Dr. Mehran Habibi, Medical Director of the Johns Hopkins Breast Center, and Dr. Susan Hoover, Surgical Oncologist for Moffitt Cancer Center’s Department of Breast Oncology, are the participating Principal Investigators (PI) for their respective centers in the trial. Johns Hopkins and Moffitt are the number one and number two highest enrolling centers in the study. Dr. Habibi, the Lead PI of the trial, will be working closely with Dr. Hoover to develop a publication cadence for this meaningful and relevant work.

"Johns Hopkins is continuously pursuing the newest technology and advancements in breast cancer diagnosis and treatment," Dr. Habibi explained. "Participating in this study has allowed us to face the challenge of positive margin rates after lumpectomy head-on."

Dr. Hoover has also spoken out about Moffitt Cancer Center’s efforts to stay on top of the latest technology for both breast cancer screening and treatment.

"Moffitt is a thought leader in the world of breast disease. We are in constant motion striving to stay ahead of the latest innovations in breast cancer in order to go beyond the current standard of care for our patients," said Dr. Hoover. "With MarginProbe’s ability to identify positive margins in real-time and potentially lower re-excision rates, participating in this Post-Approval Study put us one step closer to accomplishing this goal."

Johns Hopkins and Moffitt now join Pinnacle Health Cancer Institute, Summit Medical Group, and Northshore University HealthSystem as sites which have completed enrollment in the study. The three sites will follow each patient for six months as required in the next phase of the study. To date, over 300 of the study’s 440 patients have been enrolled. Six additional cancer centers across the country will continue accruing patients until August 2019 when enrollment is anticipated to be complete.

The adoption of MarginProbe by major cancer centers such as Johns Hopkins and Moffitt speaks volumes for the device’s credibility and efficacy, as well as the role it plays in improving the healthcare experience for patients. Nearly 200,000 women receive lumpectomy surgery annually, which precedes a period of uncertainty while awaiting final pathology results. A pathology report indicating a positive margin subjects patients to further surgery and a prolonged treatment timeline. Acceptance of MarginProbe as a Standard of Care will provide significantly more women with the peace of mind that their cancer was fully removed during one procedure, and the ability to complete their treatment plan returning them back to their normal life.

The MarginProbe device utilizes radiofrequency spectroscopy to characterize and differentiate cancerous versus healthy tissue, giving surgeons the ability to identify microscopic residual cancer and DCIS in real-time, removing additional tissue if needed. MarginProbe provides greater confidence for both the surgeon and the patient that all of the cancer is successfully removed in the first surgery and reduces the likelihood of costly, burdensome additional surgeries.

For a list of cancer centers currently enrolling patients in the MarginProbe post-approval trial, please visit www.clinicaltrials.govand search "MarginProbe".