Titan Pharmaceuticals Announces Reverse Stock Split

On December 1, 2020 Titan Pharmaceuticals, Inc. (NASDAQ: TTNP) ("Titan" or the "Company") reported that its Board of Directors has approved a 1-for-30 reverse stock split of the Company’s common stock, which will be effective at 5:00 p.m. Eastern Time on Monday, November 30, 2020 (Press release, Titan Pharmaceuticals, DEC 1, 2020, View Source [SID1234572032]). The Company’s stockholders approved the reverse stock split at a Special Meeting of Stockholders on November 30, 2020. The Company’s shares will begin trading on a split-adjusted basis on the Nasdaq Capital Market commencing upon market open on December 1, 2020.

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As a result of the reverse split, each 30 shares of the Company’s issued and outstanding common stock will be automatically combined and converted into one issued and outstanding share of common stock, par value $0.001 per share. The Company will not issue any fractional shares in connection with the reverse stock split. Instead, the number of shares will be rounded up to the next whole number. The reverse stock split will not modify the rights or preferences of the common stock.

Immediately after the reverse split becomes effective, there will be approximately 6.6 million shares of common stock issued and outstanding. The common shares will trade under a new CUSIP number, 888314606, effective December 1, 2020, and continue to trade under the symbol "TTNP." All stock options and warrants of the Company outstanding immediately prior to the reverse stock split have been proportionally adjusted.

The Company has appointed its transfer agent, Continental Stock Transfer & Trust Company ("Continental"), to act as exchange agent for the reverse stock split. Stockholders owning shares via a bank, broker or other nominee will have their positions automatically adjusted to reflect the reverse stock split and will not be required to take further action in connection with the reverse stock split, subject to brokers’ particular processes. Continental can be reached at (917) 262-2378.

Blueprint Medicines Announces FDA Approval of GAVRETO™ (pralsetinib) for the Treatment of Patients with Advanced or Metastatic RET-Mutant and RET Fusion-Positive Thyroid Cancer

On December 1, 2020 Blueprint Medicines Corporation (NASDAQ: BPMC), a precision therapy company focused on genomically defined cancers, rare diseases and cancer immunotherapy, reported that the U.S. Food and Drug Administration (FDA) has approved GAVRETO (pralsetinib) for the treatment of patients with RET-altered thyroid cancers (Press release, Blueprint Medicines, DEC 1, 2020, View Source [SID1234572031]). The accelerated approval expands the labeled indications for GAVRETO to include adult and pediatric patients 12 years of age and older with advanced or metastatic RET-mutant medullary thyroid cancer (MTC) who require systemic therapy, or with advanced or metastatic RET fusion-positive thyroid cancer who require systemic therapy and who are radioactive iodine-refractory (if radioactive iodine is appropriate). Developed by Blueprint Medicines, GAVRETO is a once-daily oral precision therapy designed to potently and selectively target RET alterations that drive multiple tumor types. GAVRETO is jointly commercialized in the U.S. by Blueprint Medicines and Genentech, a wholly owned member of the Roche Group, under Blueprint Medicines’ collaboration with Roche.

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In the Phase 1/2 ARROW trial, GAVRETO showed durable efficacy and was generally well-tolerated in patients with RET-altered thyroid cancers with or without prior systemic therapy. Earlier this year, the FDA granted accelerated approval to GAVRETO for the treatment of adults with metastatic RET fusion-positive non-small cell lung cancer (NSCLC) as detected by an FDA approved test.

"With this approval, Blueprint Medicines has achieved four marketing authorizations this year across our lead programs, making real our vision to bring transformative precision therapies to patients globally," said Jeff Albers, Chief Executive Officer of Blueprint Medicines. "Today’s approval also builds further momentum toward bringing GAVRETO to a wide range of patients with RET-altered cancers. Now, as we work with our partner Genentech to rapidly deliver GAVRETO to patients with RET-altered non-small cell lung cancer and thyroid cancers, we continue to explore the potential of GAVRETO to address additional tumor types and treatment settings."

"Traditionally, we have treated patients with RET-altered thyroid cancers with multi-kinase inhibitors, non-selective therapies with modest efficacy and clinically significant side effects. The FDA approval of pralsetinib (GAVRETO), a once-daily RET-targeted therapy, advances the standard of care for these patients," said Mimi Hu, M.D., professor in the Department of Endocrine Neoplasia and Hormonal Disorders at The University of Texas MD Anderson Cancer Center, and an investigator on the ARROW trial. "As a clinical researcher with a focus on thyroid cancer, I am encouraged by the safety profile and durable responses shown by GAVRETO in RET-altered thyroid cancers in both treatment-naïve and previously treated patients."

This approval is based on efficacy and safety results from the ARROW trial.1 In 55 patients with RET-mutant MTC previously treated with cabozantinib or vandetanib, the overall response rate (ORR) was 60 percent (95% CI: 46%, 73%), and the median duration of response (DOR) was not reached (95% CI: 15.1 months, not estimable). In 29 cabozantinib and vandetanib-naïve patients with RET-mutant MTC who were not candidates for standard systemic therapy per the study protocol, the ORR was 66 percent (95% CI: 46%, 82%), and the median DOR was not reached (95% CI: not estimable, not estimable). In addition, the ORR was 89 percent (95% CI: 52%, 100%) in nine patients with RET fusion-positive thyroid cancer, and the median DOR was not reached (95% CI: not estimable, not estimable). In ARROW trial patients across RET-altered tumor types, the most common adverse reactions (≥25%) were constipation, hypertension, fatigue, musculoskeletal pain and diarrhea.

The continued approval of GAVRETO for advanced or metastatic RET-altered thyroid cancers may be contingent upon verification and description of clinical benefit in confirmatory trials. The FDA approved these additional indications for GAVRETO under its Real-Time Oncology Review (RTOR) pilot program, which aims to explore a more efficient review process to ensure safe and effective treatments are available to patients as early as possible.

"The FDA approval of GAVRETO has the potential to address important medical needs for patients with RET-altered thyroid cancers, and reflects a shift in care toward precision medicines designed to target the underlying driver of disease," said Gary Bloom, executive director of ThyCa: Thyroid Cancer Survivors’ Association (www.thyca.org). "We are excited that the emergence of targeted therapies like GAVRETO, combined with the expanded use of biomarker testing, may dramatically improve treatment for the RET-altered thyroid cancer community. At ThyCa, we are committed to advancing awareness of these promising areas of clinical research, educating our members on the importance of biomarker testing and offering support for those impacted by the disease."

Biomarker testing for RET enables clinicians to identify patients who are candidates for treatment with GAVRETO. RET alterations can be identified with available biomarker tests, including next-generation sequencing with tumor tissue or liquid biopsies.

Blueprint Medicines is dedicated to helping patients access GAVRETO and delivering support throughout their treatment journey. As part of this commitment, Blueprint Medicines is providing YourBlueprint, a patient support program that offers access and affordability solutions for individuals receiving GAVRETO. For more information, visit YourBlueprint.com or call 1-888-BLUPRNT (1-888-258-7768), Monday to Friday, 8:00 a.m. to 8:00 p.m. ET. Healthcare providers who prescribe GAVRETO can fill out an enrollment form at YourBlueprint.com/HCP to help patients access the support services.

About GAVRETO (pralsetinib)

GAVRETO (pralsetinib) is a once-daily oral targeted therapy approved by the FDA for the treatment of three indications: adult patients with metastatic RET fusion-positive NSCLC as detected by an FDA approved test, adult and pediatric patients 12 years of age and older with advanced or metastatic RET-mutant MTC who require systemic therapy, and adults and pediatric patients 12 years of age and older with advanced or metastatic RET fusion-positive thyroid cancer who require systemic therapy and who are radioactive iodine-refractory (if radioactive iodine is appropriate).

GAVRETO is not approved for the treatment of any other indication in the U.S. by the FDA or for any indication in any other jurisdiction by any other health authority.

GAVRETO is designed to selectively and potently target oncogenic RET alterations, including secondary RET mutations predicted to drive resistance to treatment. In pre-clinical studies, GAVRETO inhibited RET at lower concentrations than other pharmacologically relevant kinases, including VEGFR2, FGFR2 and JAK2. For more information, visit GAVRETO.com.

Blueprint Medicines and Roche are co-developing GAVRETO globally (excluding Greater China) for the treatment of patients with RET-altered NSCLC, various types of thyroid cancer and other solid tumors. The European Medicines Agency validated a marketing authorization application for GAVRETO for the treatment of RET fusion-positive NSCLC. The FDA granted breakthrough therapy designation to GAVRETO for the treatment of RET fusion-positive NSCLC that has progressed following platinum-based chemotherapy and for RET mutation-positive MTC that requires systemic treatment and for which there are no acceptable alternative treatments.

Blueprint Medicines has an exclusive collaboration and license agreement with CStone Pharmaceuticals for the development and commercialization of GAVRETO in Greater China, which encompasses Mainland China, Hong Kong, Macau and Taiwan.

Enrollment is ongoing in the Phase 1/2 ARROW trial, including for patients with various RET fusion-positive solid tumors, and in the Phase 3 AcceleRET Lung trial for treatment-naïve patients with RET fusion-positive NSCLC. For more information about GAVRETO clinical trials, visit www.clinicaltrials.gov or www.blueprintclinicaltrials.com.

About RET-Altered Solid Tumors

RET activating fusions and mutations are key disease drivers in many cancer types, including NSCLC and multiple types of thyroid cancer. RET fusions are implicated in approximately 1 to 2 percent of patients with NSCLC and approximately 10 to 20 percent of patients with papillary thyroid cancer, while RET mutations are implicated in approximately 90 percent of patients with advanced MTC. In addition, oncogenic RET fusions are observed at low frequencies in colorectal, breast, pancreatic and other cancers, as well as in patients with treatment-resistant EGFR-mutant NSCLC.

Important Safety Information

Interstitial Lung Disease (ILD)/Pneumonitis occurred in 10% of patients who received GAVRETO, including 2.7% with Grade 3/4, and 0.5% with fatal reactions. Monitor for pulmonary symptoms indicative of ILD/pneumonitis. Withhold GAVRETO and promptly investigate for ILD in any patient who presents with acute or worsening of respiratory symptoms (e.g., dyspnea, cough, and fever). Withhold, reduce dose or permanently discontinue GAVRETO based on severity of confirmed ILD.

Hypertension occurred in 29% of patients, including Grade 3 hypertension in 14% of patients. Overall, 7% had their dose interrupted and 3.2% had their dose reduced for hypertension. Treatment-emergent hypertension was most commonly managed with anti-hypertension medications. Do not initiate GAVRETO in patients with uncontrolled hypertension. Optimize blood pressure prior to initiating GAVRETO. Monitor blood pressure after 1 week, at least monthly thereafter and as clinically indicated. Initiate or adjust anti-hypertensive therapy as appropriate. Withhold, reduce dose, or permanently discontinue GAVRETO based on the severity.

Hepatotoxicity: Serious hepatic adverse reactions occurred in 2.1% of patients treated with GAVRETO. Increased aspartate aminotransferase (AST) occurred in 69% of patients, including Grade 3/4 in 5% and increased alanine aminotransferase (ALT) occurred in 46% of patients, including Grade 3/4 in 6%. The median time to first onset for increased AST was 15 days (range: 5 days to 1.5 years) and increased ALT was 22 days (range: 7 days to 1.7 years). Monitor AST and ALT prior to initiating GAVRETO, every 2 weeks during the first 3 months, then monthly thereafter and as clinically indicated. Withhold, reduce dose or permanently discontinue GAVRETO based on severity.

Grade ≥ 3 hemorrhagic events occurred in 2.5% of patients treated with GAVRETO including one patient with a fatal hemorrhagic event. Permanently discontinue GAVRETO in patients with severe or life-threatening hemorrhage.

Tumor Lysis Syndrome (TLS): Cases of TLS have been reported in patients with medullary thyroid carcinoma receiving GAVRETO. Patients may be at risk of TLS if they have rapidly growing tumors, a high tumor burden, renal dysfunction, or dehydration. Closely monitor patients at risk, consider appropriate prophylaxis including hydration, and treat as clinically indicated.

Impaired wound healing can occur in patients who receive drugs that inhibit the vascular endothelial growth factor (VEGF) signaling pathway. Therefore, GAVRETO has the potential to adversely affect wound healing. Withhold GAVRETO for at least 5 days prior to elective surgery. Do not administer for at least 2 weeks following major surgery and until adequate wound healing. The safety of resumption of GAVRETO after resolution of wound healing complications has not been established.

Based on findings from animal studies and its mechanism of action, GAVRETO can cause fetal harm when administered to a pregnant woman. Advise pregnant women of the potential risk to a fetus. Advise females of

reproductive potential to use effective non-hormonal contraception during treatment with GAVRETO and for 2 weeks after the final dose. Advise males with female partners of reproductive potential to use effective contraception during treatment with GAVRETO and for 1 week after the final dose. Advise women not to breastfeed during treatment with GAVRETO and for 1 week after the final dose.

Common adverse reactions (≥25%) were constipation, hypertension, fatigue, musculoskeletal pain and diarrhea. Common Grade 3/4 laboratory abnormalities (≥2%) were decreased lymphocytes, decreased neutrophils, decreased hemoglobin, decreased phosphate, decreased calcium (corrected), decreased sodium, increased AST, increased ALT, decreased platelets and increased alkaline phosphatase.

Avoid coadministration of GAVRETO with strong CYP3A inhibitors or combined P-gp and strong CYP3A inhibitors. If coadministration cannot be avoided, reduce the GAVRETO dose. Avoid coadministration of GAVRETO with strong CYP3A inducers. If coadministration cannot be avoided, increase the GAVRETO dose.

Moleculin Announces FDA Approves 3 Rare Pediatric Disease Designations for WP1066

On December 1, 2020 Moleculin Biotech, Inc., (Nasdaq: MBRX) (Moleculin or the Company), a clinical stage pharmaceutical company with a broad portfolio of drug candidates targeting highly resistant tumors and viruses, reported that the US Food and Drug Administration (FDA) has approved its request for a "Rare Pediatric Disease" designation for its drug candidate WP1066 (Press release, Moleculin, DEC 1, 2020, View Source [SID1234572030]). The designation entitles Moleculin to receive a transferrable Priority Review Voucher (PRV) upon New Drug Approval (NDA) for each of three indications, including diffuse intrinsic pontine glioma (DIPG), medulloblastoma and atypical teratoid rhabdoid tumor.

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"The early activity we are seeing in WP1066 is both unexpected and encouraging," commented Walter Klemp, Chairman and CEO of Moleculin. "The approval of these three Rare Pediatric Disease designations is a reminder of just how important our efforts are to potentially help children with brain tumors."

Mr. Klemp concluded: "It is also important for investors to understand the implications of the PRVs or Priority Review Vouchers. These vouchers are issued upon drug approval of the rare disease indication from the FDA and, once issued, can be transferred to other drug developers. These PRVs have historically had tremendous value and have been recently sold for up to $100 million or more. For Moleculin to have the potential for three of them is noteworthy indeed."

Targovax announces impressive objective responses as well as effects on non-injected lesions in ONCOS-102 trial in anti-PD1 refractory melanoma patients

On December 1, 2020 Targovax ASA (OSE: TRVX), a clinical stage immuno-oncology company developing immune activators to target hard-to-treat solid tumors, reported that the combination of ONCOS-102 and pembrolizumab (Keytruda) has demonstrated 35% best objective response rate (ORR) in anti-PD1 refractory malignant melanoma (Press release, Targovax, DEC 1, 2020, View Source [SID1234572029]).

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In this two-part, open label phase 1 trial the combination of ONCOS-102 and the anti-PD1 checkpoint inhibitor (CPI) pembrolizumab has been tested in patients with advanced, unresectable melanoma who have had disease progression despite treatment with anti-PD1 CPI. This is a particularly challenging patient population, which is resistant to approved immunotherapies and has few treatment alternatives available.

For the trial overall, tumor responses were observed in 7 out of 20 evaluable patients treated with the ONCOS-102 and pembrolizumab combination, translating into an ORR of 35% by RECIST 1.1 criteria.

In addition, there were multiple examples of responses in non-injected lesions, including 2 patients where a non-injected lesion completely disappeared, indicating that ONCOS-102 can induce systemic anti-tumor immunity.

Prof. Jedd Wolchok, Investigator, Memorial Sloan Kettering Cancer Centre, New York said: "Checkpoint inhibitors have had a significant impact on the way we treat melanoma; however, a subset of patients still does not respond or become resistant to treatment. Therefore, there is a high medical need for immune activating agents to overcome resistance to checkpoint blockade. ONCOS-102 is one such agent that can re-sensitize patients to anti-PD1 therapy. Although these are early data, observing objective responses with some occurring in non-injected lesions in this first exploratory phase 1 trial is encouraging, and we will follow with great interest as ONCOS-102 moves forward into later-stage development."

The trial was designed with two parts assessing different dosing regimens. In Part 1, 9 patients were given 3 intra-tumoral ONCOS-102 injections during the first week, followed by systemic treatment with pembrolizumab every third week for up to 24 weeks. As reported in July 2019, preliminary tumor responses were observed in 3 out of 9 patients in at least one CT scan (see link here). 1 patient has since been determined as non-evaluable (trial inclusion criteria not met), and these numbers have now been updated to 3 out of 8 patients with ORR for Part 1.

12 more patients were enrolled in Part 2 of the trial, where an extended dosing regimen of 12 intra-tumoral ONCOS-102 injections was tested; 4 injections during the first two weeks followed by concomitant administration of ONCOS-102 and pembrolizumab from week 3 and every third week for up to 24 weeks. Tumor responses were observed in 4 out of the 12 patients in at least one CT scan. Notably, the patients in Part 2 had markedly more advanced disease than in Part 1, with the majority diagnosed as stage IV metastatic melanoma when entering the trial. Importantly, both regimens had favorable tolerability profiles, with no safety concerns.

These data are very strong compared to other therapies in development for the same indication in combination with anti-PD1 CPI, including TLR-9 agonists and other oncolytic viruses, which have reported ORR of ca. 25-30%. As such, the observed ONCOS-102 response rate and effect in non-injected lesions can be considered class-leading for the treatment of anti-PD1 refractory malignant melanoma.

Oystein Soug, Chief Executive Officer of Targovax, commented: "These impressive efficacy data in anti-PD1 refractory melanoma are the most important clinical results for Targovax to date. The data clearly confirm our hypothesis that ONCOS-102 can benefit cancer patients resistant to checkpoint inhibition by triggering local and systemic immune activation. They also provide evidence of clinical efficacy and establishes ONCOS-102 as one of the most promising combination partners to checkpoint inhibitors. We will now carefully analyze the immunological data and are planning for a confirmatory melanoma trial for the ONCOS-102 and checkpoint inhibitor combination."

The trial (NCT03003676) was conducted at three sites in the US and one site in Norway, with Memorial Sloan Kettering CC being the coordinating site.

Online presentation:

Targovax management will present the data in a live webcast 2 December 2020 at 10:00 CET. You can join the webcast here. It will be possible to ask questions during the presentation. A replay of the webcast will be available in the Investor section under "Presentations" after the event.

Avid Bioservices Declares Quarterly Dividend on Its Series E Convertible Preferred Stock

On December 1, 2020 Avid Bioservices, Inc. (NASDAQ:CDMO) (NASDAQ:CDMOP), a dedicated biologics contract development and manufacturing organization (CDMO) working to improve patient lives by providing high quality development and manufacturing services to biotechnology and pharmaceutical companies, reported that its Board of Directors has declared a quarterly cash dividend payment on the Company’s 10.50% Series E Convertible Preferred Stock (the "Series E Preferred Stock") (Press release, Avid Bioservices, DEC 1, 2020, View Source [SID1234572028]).

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The quarterly dividend on the Series E Preferred Stock is payable on January 4, 2021 to holders of record at the close of business on December 14, 2020.

The quarterly dividend payment on the Series E Preferred Stock will be $0.65625 per share, which is equivalent to an annualized 10.50% per share, based on the $25.00 per share stated liquidation preference, accruing from October 1, 2020 through December 31, 2020. The Series E Preferred Stock is listed on the NASDAQ Capital Market and trades under the ticker symbol "CDMOP".