On January 6, 2021 Autolus Therapeutics plc (Nasdaq: AUTL), a clinical-stage biopharmaceutical company developing next-generation programmed T cell therapies, updated its business outlook, strengthening its focus on its potentially transformational CAR T cell therapy candidate, AUTO1, which is being investigated in relapsed / refractory adult B-Acute Lymphoblastic Leukemia (ALL) (Press release, Autolus, JAN 6, 2021, View Source [SID1234573697]).

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"We are very excited about the unique characteristics of AUTO1 that we reported at ASH (Free ASH Whitepaper) in December 2020, with some patients continuing in molecular complete remission at 24 months without a subsequent transplant, an event-free survival of 52% at 12 months and a well-tolerated safety profile. Taking into consideration the high unmet need in adult ALL and the commercial opportunity this represents, we are prioritizing this program with potential pivotal data expected in 2022," said Dr. Christian Itin, chairman and chief executive officer of Autolus. "We also plan to capitalize on the differentiated profile of AUTO1 by exploring activity in additional B-cell malignancies, including Primary CNS Lymphoma (PCNSL) where no adequate standard of care currently exists. We expect to see first data from these additional indications in 2021."

Additional clinical data points in 2021 are expected from AUTO1/22, a novel dual targeting CAR T cell based therapy candidate based on AUTO1, with the first pediatric ALL patient dosed in December 2020, and AUTO4 in Peripheral T Cell Lymphoma (PTCL), which will continue in 2021 through a dose escalation phase. Furthermore, the company continues to progress its pipeline of next generation programs, including for solid tumor indications, in collaboration with its academic partners.

With the prioritization of the AUTO1 program, the company plans to seek a partner for the AUTO3 program, its CD19 and CD22 dual targeting CAR T product candidate being investigated in relapsed/refractory diffuse large B cell lymphoma (DLBCL), before progressing the program into the next phase of development. In addition, through Q1 2021, the company will adjust its workforce and infrastructure footprint, which will involve an overall reduction in headcount of approximately 20%. The company expects to realize cash savings, on an annualized basis, of approximately $15 million per annum once the operational changes are fully implemented. Additionally, the company announced a reorganization of its management team. David Brochu was promoted to Chief Technical Officer (CTO) with expanded responsibilities from Senior Vice President, Product Delivery. Senior Vice Presidents Dr. Adam Hacker and Dr. Nushmia Khokhar will be leaving the company in Q1 2021. A search for a new Chief Medical Officer is ongoing.

"Building on its differentiated clinical profile, we believe AUTO1 is well positioned to deliver fundamental value for patients and shareholders. Our organizational focus will position us well to realize the potential of AUTO1 and lay the foundation for the next opportunities in our pipeline with several clinical proof of concepts targeted during 2021 and 2022," said Dr. Christian Itin, chairman and chief executive officer of Autolus.

On January 6, 2021 Atara Biotherapeutics, Inc. (Nasdaq: ATRA), a pioneer in T-cell immunotherapy, leveraging its novel allogeneic EBV T- cell platform to develop transformative therapies for patients with serious diseases including solid tumors, hematologic cancers and autoimmune diseases, reported that Pascal Touchon, President and Chief Executive Officer, will present at the 39th Annual J.P. Morgan Healthcare Conference on Wednesday, January 13 at 1:30 PM PST/4:30 PM EST (Press release, Atara Biotherapeutics, JAN 6, 2021, View Source [SID1234574480]).

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A live audio webcast of the presentation will be available by visiting the Investor Events and Presentations section of atarabio.com. An archived replay of the webcast will be available on the Company’s website for 30 days following the live presentation.

On January 6, 2021 Elevation Oncology, a clinical-stage biopharmaceutical company focused on the development of precision medicines for patients with genomically defined cancers, reported that Shawn M. Leland, PharmD, RPh, Founder and Chief Executive Officer of Elevation Oncology, will present at the 39th Annual J.P. Morgan Healthcare Conference on Tuesday, January 12, 2021 at 3:45 p.m. ET (Press release, Elevation Oncology, JAN 6, 2021, View Source;utm_medium=rss&utm_campaign=elevation-to-present-at-39th-annual-j-p-morgan-2021 [SID1234574448]).

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On January 6, 2021 Dana-Farber Cancer Institute and Mass General Cancer Center reported that have created molecular ON-OFF switches to regulate the activity of CAR T cells, a potent form of cell-based immunotherapy that has had dramatic success in treating some advanced cancers, but which pose a significant risk of toxic side effects (Press release, Dana-Farber Cancer Institute, JAN 6, 2021, View Source [SID1234573760]).

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CAR T cells are immune cells genetically modified to recognize and attack tumors cells. Once given, these "living drugs" proliferate and kill tumor cells over weeks to months, in some cases causing life-threatening inflammatory reactions that are difficult to control. In this way, CAR T cells are unlike more established forms of cancer therapy – chemotherapy or radiotherapy for instance – whose dose can be precisely tuned up or down over time.

The scientists reported in Science Translational Medicine the development of switchable CAR T cells that can be turned on or off by giving a commonly used cancer drug, lenalidomide. In the laboratory, the researchers designed OFF-switch CAR T cells that could be quickly, reversibly turned off by administering the drug, after which the CAR T cells recovered their anti-tumor activity. Separately, the researchers also reported ON-switch CAR T cells that only killed tumor cells during lenalidomide treatment.

In the future, switchable cell therapies might allow patients with their physicians to take a pill – or not – to tune the amount of CAR T cell activity from day to day, hopefully reducing toxic side effects.

"From the start, our goal was to build cancer therapies that are less hard on people. Having built these switches using human genetic sequences and an FDA-approved drug, we are excited for the potential to translate this research to clinical use," said Max Jan, MD, PhD, first author of the report. He is affiliated with the laboratories of Benjamin Ebert, MD, PhD, and Marcela Maus, MD, PhD, the report’s senior authors. Other authors include researchers from the Broad Institute of MIT and Harvard, and Harvard Medical School.

CAR T cells are created by harvesting immune T cells from the patient and reprogramming them in the laboratory to produce a finely-tuned receptor molecule, termed a CAR (for chimeric antigen receptor), that recognizes a distinctive protein on the surface of the patient’s cancer cells. The CAR T cells, after being engineered in the lab and returned to the patient, circulate through the body and home in on the cancer cells by binding to the distinctive surface protein they have been engineered to recognize. This binding event stimulates an immune attack, destruction of the cancer cells, and proliferation of the CAR T cells.

A drawback, however, is that uncontrolled proliferation of the CAR T cells sometimes triggers cytokine release syndrome (CRS), the release of inflammation-causing signals throughout the body that can cause toxicities ranging from mild fever to life-threatening organ failure. Current management of these toxic reactions relies on intensive care unit support and drugs including immunosuppressive corticosteroids, while many researchers are trying to develop methods of controlling the activity of CAR T cells in order to prevent these toxic side effects.

"CAR T cells can be fantastically effective therapies, but they can also have serious toxicities and can cause significant morbidity and mortality," said Ebert who is Chair of Medical Oncology at Dana-Farber. "They are currently difficult to control once administered to the patient."

CAR T cell therapy has had most success in blood cancers. Three CAR T agents have been approved: Kymriah for children and young adults with B-cell precursor acute lymphoblastic leukemia (ALL), both Kymriah and Yescarta for treatment of adults with diffuse large B-cell lymphoma and Tecartus for adults with mantle cell lymphoma. Scientists are investigating an array of different approaches with the aim of extending the reach of CAR T therapies to other blood cancers and to solid tumors, if a number of hurdles can be overcome, including the problem of treatment toxicity.

To create the ON and OFF switch systems for CAR T cells, the scientists used a relatively new technique known as targeted protein degradation. It exploits a mechanism that cells use to dispose of unwanted or abnormal proteins; the proteins are marked for destruction by a structure within cells that acts like a garbage disposal. A small number of drugs, including lenalidomide, act by targeting specific proteins for degradation using this pathway.

The researchers used this technique to engineer small protein tags that are sent to the cellular garbage disposal by lenalidomide. When this degradation tag was affixed to the CAR, it allowed the tagged CAR to be degraded during drug treatment, thereby stopping T cells from recognizing cancer cells. Because CAR proteins are continually manufactured by these engineered T cells, after drug treatment new CAR proteins accumulate and restore the cell’s anti-tumor function. The researchers propose that the switch system might in the future allow patients to have their CAR T cell treatment temporarily paused to prevent short-term toxicity and still have long-term therapeutic effects against their cancer.

The scientists also built an ON-switch CAR by further engineering the proteins that physically interact with lenalidomide. This system has the potential to be especially safe, because the T cells only recognize and attack tumor cells during drug treatment. If used to treat cancers such as multiple myeloma that are sensitive to lenalidomide, ON-switch CAR T cells could allow for a coordinated attack by the immune cells and the drug that controls them.

"The long-term goal is to have multiple different drugs that control different on and off switches" so that scientists can develop "ever-more complex cellular therapies," explained Ebert.

This work was supported by the National Institutes of Health grants (R01HL082945, P01CA108631, and P50CA206963), the Howard Hughes Medical Institute, the Edward P. Evans Foundation, and the Leukemia and Lymphoma Society.

On January 6, 2021 Harpoon Therapeutics, Inc. (Nasdaq: HARP), reported the pricing of an underwritten public offering of 5,882,352 shares of its common stock at a price to the public of $17.00 per share (Press release, Harpoon Therapeutics, JAN 6, 2021, View Source [SID1234573634]). Harpoon Therapeutics expects that the gross proceeds from the sale of the shares will be approximately $100.0 million, before deducting underwriting discounts and commissions and offering expenses payable by Harpoon Therapeutics. In addition, Harpoon Therapeutics has granted the underwriters in the offering a 30-day option to purchase up to 882,352 additional shares of common stock at the public offering price. The offering is expected to close on January 11, 2021, subject to customary closing conditions.

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Harpoon Therapeutics plans to use the net proceeds of the offering, together with other available funds, to fund the continued clinical development of HPN424 in metastatic castration-resistant prostate cancer, HPN536 in ovarian cancer and other solid tumors, HPN217 in multiple myeloma, and HPN328 for the treatment of small cell lung cancer and other neuroendocrine tumors expressing Delta-like canonical Notch ligand 3; to advance the development of other pipeline candidates, including HPN601; and for working capital and general corporate purposes.

SVB Leerink and Piper Sandler are acting as joint bookrunning managers for the offering. Baird and Truist Securities are acting as co-lead managers for the offering. Roth Capital Partners is acting as co-manager for the offering.

The shares of common stock are being offered pursuant to a "shelf" registration statement previously filed with and declared effective by the Securities and Exchange Commission (SEC). Harpoon Therapeutics has filed a preliminary prospectus supplement and the accompanying prospectus related to the offering with the SEC, which are available on the SEC’s website, located at www.sec.gov. Copies of the final prospectus supplement relating to this offering, when available, and the accompanying prospectus 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] or Piper Sandler & Co., Attention: Prospectus Department, 800 Nicollet Mall, J12S03, Minneapolis, MN 55402, by telephone at (800) 747-3924 or by email at [email protected].

This press release shall not constitute an offer to sell, or a solicitation of an offer to buy, 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. Any offer, if at all, will be made only by means of a prospectus supplement and accompanying prospectus, which are a part of the effective registration statement.