On February 2, 2022 Titan Pharmaceuticals, Inc. (NASDAQ: TTNP) ("Titan" or the "Company") reported that it has entered into a securities purchase agreement with a single institutional investor to purchase 3,374,242 shares of its common stock (or pre-funded warrants in lieu thereof) in a registered direct offering priced at-the-market under Nasdaq rules (Press release, Titan Pharmaceuticals, FEB 2, 2022, View Source [SID1234607648]). In a concurrent private placement, Titan has also agreed to issue and sell to the investor 1,289,796 pre-funded warrants, at the same purchase price as in the registered direct offering. In addition, the Company has agreed to issue to the investor in a concurrent private placement unregistered warrants to purchase up to an aggregate of 4,664,038 shares of common stock. The combined offering price of each share or pre-funded warrant and each warrant will be $1.18. The warrants will be immediately exercisable, will expire on the five year and six month anniversary of the issuance date and will have an exercise price of $1.14 per share.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

The aggregate gross proceeds to the Company of both offerings is expected to be approximately $5.5 million. The offerings are expected to close on or about February 4, 2022, subject to the satisfaction of customary closing conditions.

Maxim Group LLC is acting as the exclusive placement agent in connection with the offerings.

The shares of common stock (or pre-funded warrants in lieu thereof) in the registered direct offering are being offered pursuant to a shelf registration statement on Form S-3 (File No. 333-230742), which was declared effective by the United States Securities and Exchange Commission ("SEC") on April 24, 2019. The pre-funded warrants and warrants issued in the concurrent private placement and the shares issuable upon exercise of such warrants were offered in a private placement under Section 4(a)(2) of the Securities Act of 1933, as amended (the "Act"), and Regulation D promulgated thereunder and have not been registered under the Act or applicable state securities laws.

This press release does not constitute an offer to sell or the solicitation of an offer to buy, nor will there be any sales of these securities in any jurisdiction in which such offer, solicitation or sale would be unlawful prior to registration or qualification under the securities laws of such jurisdiction. A prospectus supplement relating to the shares of common stock (or pre-funded warrants in lieu thereof) issued in the registered direct offering will be filed by Titan with the SEC. When available, copies of the prospectus supplement relating to the registered direct offering, together with the accompanying prospectus, can be obtained at the SEC’s website at www.sec.gov or from Maxim Group LLC, 300 Park Avenue, New York, NY 10022, Attention: Syndicate Department, or via email at [email protected] or telephone at (212) 895-3745.

On February 2, 2022 Pimera Therapeutics, Inc., a clinical-stage biotechnology company focused on developing breakthrough medicines for cancer and other diseases with high unmet medical need, reported that the Company and its collaborators Dr. Luc Furic, Head, Translational Prostate Cancer Research at Peter MacCallum Cancer Centre and Professor Ross Hannan, Centenary Chair in Cancer Research and Head of the ACRF Department of Cancer Biology and Therapeutics, Associate Dean Research (Biomedical and Translational) at Australian National University, have been awarded a Prostate Cancer Research Program (PCRP) grant from the Department of Defense to advance its lead program PMR-116 to the clinic for prostate cancer (Press release, Pimera Therapeutics, FEB 2, 2022, View Source [SID1234607653]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Pimera is developing PMR-116, a novel inhibitor of RNA polymerase I (Pol I), a transcription factor for MYC driven cancers, for the treatment of multiple solid tumor oncology indications. The grant award, which totals more than $1 million, will support efficacy studies of PMR-116 in patient-derived models, identification of novel combination therapies, and identification of biomarkers of response from the ongoing Phase 1 study of PMR-116.

"PMR-116 is a very exciting program with a novel mechanism of action and an encouraging efficacy and safety profile to date. In preclinical studies, we observed robust efficacy in several MYC-driven models, including those that are resistant to standard-of-care therapy. In the ongoing Phase 1 study, PMR-116 demonstrated favorable target engagement and early clinical efficacy signals in multiple solid tumor patients," said Mustapha Haddach, Ph.D., President and CEO of Pimera. "This recognition from the DOD on the potential of PMR-116 further validates our approach with PMR-116 to improve care for cancer patients, and in particular, prostate cancer, which is one of the leading causes of cancer death in men in the US. We look forward to advancing PMR-116 through dose escalation, expanding into additional indications, and into Phase 2 to address several large cancer markets and improve patient outcomes."

"PMR-116 suppresses the ability of cancer cells to synthesize the machinery required to express the high level of proteins required for cancer growth. What we’ve demonstrated in pre-clinical models of CRPC and NEPC with PMR-116 is a powerful new way to inhibit proliferation in the most advanced stages of prostate cancer," added Dr. Luc Furic, Head, Translational Prostate Cancer Research at Peter MacCallum Cancer Centre. "The significant support from this DOD Award will allow us to further characterize biomarkers of response to PMR-116 and perform the ground word required to bring PMR-116 to the clinic for prostate cancer patients."

This grant was supported by the Department of Defense of the U.S. Army Medical Research Acquisition under Award Number FY21-PCRP-TSA. The content is solely the responsibility of the authors and does not necessarily represent the official views of the Department of Defense.

About PMR-116
PMR-116 is our lead therapeutic in clinical development for multiple cancer indications including solid tumors. PMR-116 acts through a novel mechanism of action, targeting the RNA polymerase I, or POL I, a transcription factor for MYC driven cancers and other diseases with high unmet medical need. In preclinical studies, PMR-116 has demonstrated robust preclinical efficacy in multiple MYC-driven models, including those that are resistant to standard-of-care treatments. PMR-116 is currently in the dose escalation stage of a Phase 1a/b clinical trial being conducted in Australia. Pimera intends to expand the development of PMR-116 in patients with MYC overexpressing solid tumors in a tumor type-agnostic approach. For more information about the ongoing clinical trial, please visit ANZCTR.

On February 2, 2022 Jazz Pharmaceuticals plc (Nasdaq: JAZZ) reported that the Company has completed the submission of a Supplemental Biologics License Application (sBLA) to the U.S. Food and Drug Administration (FDA) seeking approval for a Monday/Wednesday/Friday (M/W/F) intramuscular (IM) dosing schedule for Rylaze (asparaginase erwinia chrysanthemi (recombinant)-rywn), for use as a component of a multi-agent chemotherapeutic regimen for the treatment of acute lymphoblastic leukemia (ALL) and lymphoblastic lymphoma (LBL) in adult and pediatric patients one month and older who have developed hypersensitivity to E. coli-derived asparaginase (Press release, Jazz Pharmaceuticals, FEB 2, 2022, View Source [SID1234607651]). The submission will be reviewed under the Real-Time Oncology Review (RTOR) program, an initiative of FDA’s Oncology Center of Excellence designed for efficient review of safe and effective cancer treatments, and follows Rylaze’s initial approval under the RTOR program in June 2021.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"We were pleased Rylaze, a much-needed therapeutic option, was approved under the RTOR program while the clinical trial was ongoing. Our science-led and patient-focused development program has enabled us to deliver a clinically significant advancement for patients," said Rob Iannone, M.D., M.S.C.E., executive vice president, global head of research and development of Jazz Pharmaceuticals. "With a dosing schedule of Rylaze administered 25/25/50 mg/m2 on Monday/Wednesday/Friday, patients maintain a clinically meaningful level of nadir serum asparaginase activity through the entire duration of treatment. We look forward to submitting two additional regulatory applications this year to ensure as many patients as possible can have access to a reliable and high-quality supply of this important therapy, including another regulatory application to FDA to support the intravenous route of administration and an additional application in Europe later this year."

The sBLA submitted by Jazz is supported by data from the three-cohort intramuscular administration part of the Phase 2/3 trial of Rylaze in adult and pediatric patients with ALL and LBL who have developed hypersensitivity to an E. coli-derived asparaginase. The trial studied three dosing regimens of Rylaze, with cohort 1a receiving 25 mg/m2 administered M/W/F, cohort 1b receiving 37.5 mg/m2 administered M/W/F and cohort 1c receiving 25 mg/m2 administered Monday and Wednesday and 50 mg/m2 administered on Friday. Initial results showed that in cohort 1c, a dosing regimen of Rylaze administered 25 mg/m2 on Monday and Wednesday and 50 mg/m2 on Friday demonstrated a positive benefit-to-risk profile, showing that Rylaze maintains a clinically meaningful level of nadir serum asparaginase activity (NSAA) ≥0.1 IU/mL at both 48 and 72 hours (from Friday to Monday). In addition, the safety profile of Rylaze was consistent with the reported safety information for patients with ALL/LBL receiving asparaginase with combination chemotherapy. Initial results from the trial were presented at the 63rd American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting in December 2021.1

The sBLA follows FDA approval of Rylaze in June 2021 under the RTOR program.2 Rylaze was also granted orphan drug designation for the treatment of ALL/LBL in June 2021 and was added to the National Comprehensive Cancer Network Clinical Practice Guidelines in Oncology (NCCN Guidelines) in July 2021.3

About Rylaze (asparaginase erwinia chrysanthemi (recombinant)-rywn)
Rylaze, also known as JZP458, is approved in the U.S. for use as a component of a multi-agent chemotherapeutic regimen for the treatment of acute lymphoblastic leukemia (ALL) and lymphoblastic lymphoma (LBL) in adult and pediatric patients one month or older who have developed hypersensitivity to E. coli-derived asparaginase. Rylaze has orphan drug designation for the treatment of ALL/LBL in the United States. Rylaze is a recombinant erwinia asparaginase that uses a novel Pseudomonas fluorescens expression platform. JZP458 was granted Fast Track designation by the U.S. Food and Drug Administration (FDA) in October 2019 for the treatment of this patient population. Rylaze was approved as part of the Real-Time Oncology Review program, an initiative of the FDA’s Oncology Center of Excellence designed for efficient delivery of safe and effective cancer treatments to patients.

The full U.S. Prescribing Information for Rylaze is available at: View Source

Important Safety Information

RYLAZE should not be given to people who have had:

Serious allergic reactions to RYLAZE
Serious swelling of the pancreas (stomach pain), serious blood clots, or serious bleeding during previous asparaginase treatment
RYLAZE may cause serious side effects, including:

Allergic reactions (a feeling of tightness in your throat, unusual swelling/redness in your throat and/or tongue, or trouble breathing), some of which may be life-threatening
Swelling of the pancreas (stomach pain)
Blood clots (may have a headache or pain in leg, arm, or chest)
Bleeding
Liver problems
Contact your doctor immediately if any of these side effects occur.

Some of the most common side effects with RYLAZE include: liver problems, nausea, bone and muscle pain, tiredness, infection, headache, fever, allergic reactions, fever with low white blood cell count, decreased appetite, mouth swelling (sometimes with sores), bleeding, and too much sugar in the blood.

RYLAZE can harm your unborn baby. Inform your doctor if you are pregnant, planning to become pregnant, or nursing. Females of reproductive potential should use effective contraception (other than oral contraceptives) during treatment and for 3 months following the final dose. Do not breastfeed while receiving RYLAZE and for 1 week after the final dose.

Tell your healthcare provider if there are any side effects that are bothersome or that do not go away.

These are not all the possible side effects of RYLAZE. For more information, ask your healthcare provider.

You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch, or call 1-800-FDA-1088 (1-800-332-1088).

About Acute Lymphoblastic Leukemia (ALL)
ALL is a cancer of the blood and bone marrow that can progress quickly if not treated.4 Leukemia is the most common cancer in children, and about three out of four of these cases are ALL.5 Although it is one of the most common cancers in children, ALL is among the most curable of the pediatric malignancies due to recent advancements in treatment.6,7 Adults can also develop ALL, and about four of every 10 cases of ALL diagnosed are in adults.5 The American Cancer Society estimates that almost 6,000 new cases of ALL will be diagnosed in the United States in 2021.5 Asparaginase is a core component of multi-agent chemotherapeutic regimens in ALL.8 However, asparaginase treatments derived from E. coli are associated with the potential for development of hypersensitivity reactions.9

About Lymphoblastic Lymphoma (LBL)
LBL is a rare, fast-growing, aggressive subtype of Non-Hodgkin’s lymphoma, most often seen in teenagers and young adults.10 LBL is a very aggressive lymphoma – also called high-grade lymphoma – which means the lymphoma grows quickly with early spread to different parts of the body.11,12

On February 2, 2022 Theseus Pharmaceuticals, Inc. (Theseus) (NASDAQ: THRX), a clinical-stage biopharmaceutical company focused on improving the lives of cancer patients through the discovery, development and commercialization of transformative targeted therapies, reported that the U.S. Food and Drug Administration (FDA) has granted orphan drug designation (ODD) to the company’s lead candidate THE-630, a small-molecule oral pan-variant KIT inhibitor, for the treatment of patients with advanced gastrointestinal stromal tumors (GIST) (Press release, Theseus Pharmaceuticals, FEB 2, 2022, View Source [SID1234607650]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"We are pleased to have received ODD for THE-630 so quickly after the initiation of the first-in-human trial. This designation from the FDA emphasizes the need to bring better therapeutic options to patients with advanced GIST," said David Kerstein, M.D., Chief Medical Officer at Theseus. "For patients living with GIST, progression through standard lines of therapy is often associated with the emergence of resistance mutations in KIT. We look forward to evaluating the clinical potential of THE-630 to inhibit these resistance mutations in patients who’ve exhausted available therapies and when used in earlier lines of therapy."

The FDA’s Office of Orphan Products Development grants ODD status to drugs and biologics intended for the safe and effective treatment, diagnosis or prevention of rare diseases or conditions affecting fewer than 200,000 people in the United States. ODD provides benefits to drug developers designed to support the development of drugs and biologics for small patient populations with unmet medical needs. These benefits include assistance in the drug development process, tax credits for qualified clinical costs, exemptions from certain FDA fees and seven years of marketing exclusivity.

About GIST
GIST is the most common sarcoma of the gastrointestinal tract with an estimated 4,000 to 6,000 new cases diagnosed in the United States each year. Approximately eighty percent of GIST cases are driven by mutations that activate the kinase activity of the receptor tyrosine kinase KIT, and up to ninety percent of all cases of progression are driven by secondary resistance mutations in KIT.

On February 2, 2022 Immunic, Inc. (Nasdaq: IMUX), a clinical-stage biopharmaceutical company developing a pipeline of selective oral immunology therapies focused on treating chronic inflammatory and autoimmune diseases, reported that the company received a Notice of Allowance from the U.S. Patent and Trademark Office (USPTO) for patent application 16/644581, entitled, "IL-17 and IFN-gamma inhibition for the treatment of autoimmune diseases and chronic inflammation" (Press release, Immunic, FEB 2, 2022, View Source [SID1234607647]). The company also received notice of allowance of patent application EP18762111.5 in Europe, and notice of grant of patent application 2018330633 in Australia. All three patents cover composition-of-matter of IMU-935 and related formulations, and are expected to provide protection into at least 2038, without accounting for potential Patent Term Extension (PTE) in the United States or Supplementary Protection Certificates (SPC) in Europe, respectively.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"We believe IMU-935 is a highly potent and selective oral inhibitor of IL-17, which so far, has shown a remarkably differentiated safety and tolerability profile. Allowance of composition-of-matter patents for this molecule in the United States, Europe and Australia, each with significant lifespan, is incredibly important as we continue to advance IMU-935 through the clinic," stated Daniel Vitt, Ph.D., Chief Executive Officer and President of Immunic. "This is especially true on the heels of our recently announced positive results from the single and multiple ascending dose parts of the phase 1 clinical trial of IMU-935, and the ongoing part C in moderate-to-severe psoriasis patients. Additionally, our ongoing phase 1 clinical trial of IMU-935 in patients with metastatic castration-resistant prostate cancer continues to enroll patients and we look forward to receiving initial clinical data from this indication as well."

About IMU-935
IMU-935 is a highly potent and selective inverse agonist of RORγ/RORγt (retinoic acid receptor-related orphan nuclear receptor gamma / truncated). The nuclear receptor RORγt is believed to be the main driver for the differentiation of Th17 cells and the release of cytokines involved in various inflammatory and autoimmune diseases. This target is believed to be an attractive alternative to approved antibodies for targets, such as IL-23, the IL-17 receptor and IL-17 itself. IMU-935 showed strong cytokine inhibition targeting both Th1 and Th17 responses in preclinical testing, as well as indications of activity in animal models for psoriasis, graft versus host disease, multiple sclerosis and inflammatory bowel disease. Preclinical experiments indicated that, while leading to a potent inhibition of Th17 differentiation and cytokine secretion, IMU-935 did not affect thymocyte maturation. IMU-935 is an investigational drug product that has not been approved in any jurisdiction.