On September 24, 2021 Celldex Therapeutics, Inc. (NASDAQ:CLDX) reported that senior management will participate in a fireside chat at the 2021 Cantor Virtual Global Healthcare Conference on Wednesday, September 29, 2021 at 1:20 p.m. ET (Press release, Celldex Therapeutics, SEP 24, 2021, View Source [SID1234590258]).

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A webcast of the presentation will be available on the "Events & Presentations" page of the "Investors & Media" section of the Celldex website. A replay will be available for 30 days following the event.

On September 24, 2021 Tiziana Life Sciences plc ("Tiziana", LSE: TILS, NASDAQ: TLSA), a biotechnology company a biotechnology company focused on innovative therapeutics for oncology, inflammation, and infectious diseases reported its interim results for the six months ended 30 June 2021 (Press release, Tiziana Life Sciences, SEP 24, 2021, View Source [SID1234590256]).

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Highlights during the period:

CLINICAL PROGRAMMES

Foralumab
TZLS-401

Announced an update on further analysis of lymphocyte subsets from blood samples from a Phase 1 study with nasally administered Foralumab in healthy volunteers. Results exhibiting statistically significant immunomodulatory effects on CD8 cytotoxic T-lymphocytes and other inflammatory biomarkers were observed. Systemic levels of Foralumab were below the lower quantitation limit of 8 ng/mL suggesting that nasally administered Foralumab appears to exert its effects via nasal epithelium utilizing local and lymphatic immune systems directly. These data support other clinical and pre-clinical studies showing that this route of administration is capable of inducing site-targeted immunomodulation and anti-inflammatory effects. Furthermore these pharmacodynamic data point to a clinical dose range that Tiziana intends to test in further clinical development among MS patients.

Announced positive data from the exploratory clinical study in Brazil investigating nasally administered Foralumab, its proprietary anti-CD3 human monoclonal antibody, either alone or in combination with orally administered dexamethasone ("Dexa") in COVID-19 patients. The clinical study was completed in collaboration with scientific teams at the Harvard Medical School (Boston, USA), and INTRIALS, a full-service Latin American CRO based in São Paulo, Brazil. The objectives of the trial were to assess safety of the treatment and to evaluate if progression of the diseases is delayed with nasally administered 100mcg/day Foralumab (50mcg/nostril). This study enrolled 39 patients randomized in three cohorts: cohort 1, control with no treatment (n=16); cohort 2; nasally administered Foralumab plus 3 days of priming with orally administered 6 mg Dexamethasone (n=11) and cohort 3; nasally administered Foralumab (n=12). The Foralumab treatment regimen was once a day dosing for 10 consecutive days There were no significant differences between cohort 2 and 3. All treatments were well-tolerated. There were no grade 3 or 4 severe adverse events ("SAEs") in any of the cohorts. The CT scans of the lungs showed the improvement was approximately double that shown in patients treated with Foralumab as compared to those in the control group. The results of the study were published in the peer-reviewed journal, Frontiers in Immunology entitled "Nasal Administration of Anti-CD3 Monoclonal Antibody (Foralumab) Reduces Lung Inflammation and Blood Inflammatory Biomarkers in Mild to Moderate COVID-19 Patients: A Pilot Study" in August 2021.

Signed an agreement with FHI CRO to conduct a follow-up, "proof of concept" Phase 2 study in hospitalized patients with severe COVID-19 and lung inflammation that is planned to begin in Q4 2021. Foralumab will be delivered intranasally using a metered dose delivery device.

Announced that the first patient with secondary progressive multiple sclerosis (SPMS) was dosed with nasally administered Foralumab at the Brigham and Women’s Hospital (BWH), Harvard Medical School, Boston, MA. Nasal Foralumab 50 mcg (25 mcg/nostril) was administered in 3-week cycles, with 3 times/week dosing for the first 2 weeks followed by 1 week of rest period. This first-ever clinical study in SPMS patients, under an Individual Patient Expanded Access IND, will continue for six months to evaluate routine safety, tolerability, and neurological behaviors. The study will also examine microglial activation, by positron emission tomography (PET), immunological and neurodegenerative markers to assess clinical responses following the treatment regimen.
Anti IL-6R mAb
TZLS-501, formerly NI-1201​

Working with Sciarra Laboratories to evaluate two hand-held nebulizer devices for use in the study and characterizing physical/performance characteristics. Once a device has been selected, a few candidate formulations of anti-IL6R mAb, from formulation development studies at STC Biologics, will be manufactured at small scale and evaluated using the devices.

Engaged ITR Laboratories in Canada to complete inhalation safety toxicology studies in Cynomolgous monkeys using the purified, characterized anti-IL6R mAb test item. Results from the study will be used to establish dosing for a Phase 1 study in healthy volunteers. Additional parenteral administration safety toxicology studies are in progress at ITR Laboratories to support clinical studies for treatment of autoimmune and inflammatory diseases.
Milciclib
TZLS-201

​Announced that it had executed an agreement with Takanawa Japan K.K, Pharma Team, (Takanawa) for a strategic business development plan to Identify a clinical partner in Japan and other Asian countries for further clinical development of Milciclib for treatment in advanced hepatocellular carcinoma (HCC) patients. HCC is the most common type of liver cancer and affects approximately 200,000 people per year.
Intellectual Property

As of September 2021, the Company has a total of 306 granted patents, 281 foreign and 25 US patents.
New appointments

Appointed Dr. Neil Graham MBBS, MD, MPH as Chief Medical Officer, Dr. Thomas Adams Ph.D. as Head of Drug Development and an executive director and Dr. Kevin Schutz, PharmD, as Vice-President of Regulatory Affairs.
Highlights post period end:

On September 2, 2021, Tiziana and Precision Biosciences announced an exclusive license agreement to explore Tiziana’s foralumab as an agent to induce tolerance of allogeneic CAR T cells to potentially improve the clinical outcome of CAR T cell therapy. Precision’s approach to manufacturing produces CAR T cells that are virtually CD3-negative. Foralumab will be used as a lymphodepletion or tolerizing agent, either alone or in combination with other co-stimulatory molecules, to improve the long-term survival of CAR T cells in cancer treatment.

Tiziana has formally commenced its strategic plan to change its corporate structure by establishing Tiziana Life Sciences Ltd, a Bermuda-incorporated company, as the ultimate parent company of the of the Tiziana Group. The reorganisation will be achieved by a scheme of arrangement under Part 26 of the Companies Act 2006.
FINANCIAL

For the six months to 30 June 2020 the consolidated Group made a loss of £12.59m (six months to 30 June 2020: £3.9m).

The Group ended the period with £38.6m cash as at 30 June 2021 (31 December 2020: £48.2m).
Research and development (R&D) expenses increased to £12.6m compared to £3.9m in the first half of 2020. The increase is primarily expenses related to the advancement of our proprietary programs, TZLS-401 and TZLS-501.

The Company cancelled the admission of its Ordinary Shares to trading on AIM and admitted its shares to trading on the main market for listed securities (of London Stock Exchange plc in January 2021.
The Company continues to carefully manage its working capital position and continues the process, as referred to below, to evaluate opportunities to raise further funds through the issue of additional equity capital.

To view the complete Interim Accounts click here: View Source

On September 24, 2021 Leap Therapeutics, Inc. (Nasdaq:LPTX), a biotechnology company focused on developing targeted and immuno-oncology therapeutics, reported the closing of a public offering of 27,568,072 shares of its common stock, which includes the sale of an additional 4,740,000 shares of its common stock pursuant to the full exercise of the underwriters’ option to purchase additional shares, and of pre-funded warrants to purchase 8,771,928 shares of its common stock (Press release, Leap Therapeutics, SEP 24, 2021, View Source [SID1234590255]). The gross proceeds to Leap from this offering were approximately $104 million, including $7.25 million invested by our collaborator and existing investor BeiGene, Ltd., before deducting underwriting discounts and commissions and other estimated offering expenses payable by Leap.

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Piper Sandler & Co., Raymond James & Associates, Inc. and Mizuho Securities USA LLC acted as book-running managers for the offering. Robert W. Baird & Co. Incorporated acted as lead manager for the offering.

The securities were offered and sold pursuant to an effective shelf registration statement on Form S-3 (File No. 333-248797) that was previously filed by Leap with the Securities and Exchange Commission (the "SEC") on September 14, 2020 and was declared effective by the SEC on October 16, 2020. A final prospectus supplement and the related prospectus have been filed with the SEC and are available for free on the SEC’s website at View Source Copies of the final prospectus supplement and the accompanying prospectus relating to the offering, when available, may also be obtained from Piper Sandler & Co., 800 Nicollet Mall, J12S03, Minneapolis, MN, 55402, Attention: Prospectus Department, by telephone at (800) 747-3924 or by e-mail at [email protected]. These documents may also be obtained from Raymond James & Associates, Inc., Attention: Equity Syndicate, 880 Carillon Parkway, St. Petersburg, Florida 33716, by telephone at (800) 248-8863, or by e-mail at [email protected]; or from Mizuho Securities USA LLC, Attention: Equity Capital Markets, 1271 Avenue of the Americas, 3rd Floor, New York, NY, 10020, by telephone at (212) 205-7600, or by e-mail 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.

On September 24, 2021 Targovax ASA (OSE: TRVX), a clinical stage immuno-oncology company developing immune activators to target hard-to-treat solid tumors, reported that the European Patent Office has granted EU Patent no EP3402889 (Press release, Targovax, SEP 24, 2021, View Source [SID1234590250]). The patent covers the use of ONCOS-102 in combination with chemotherapy in malignant pleural mesothelioma.

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Torbjørn Furuseth, Chief Financial Officer of Targovax, said: "We are delighted that this EU patent has been granted, further strengthening Targovax’s intellectual property portfolio. The 24-month data from our ONCOS-102 trial in mesothelioma demonstrates encouraging survival data in this area of large medical need. Securing this patent protects our innovative oncolytic immunotherapy platform and strengthens our future market position."

Targovax’s lead product candidate, ONCOS-102, is a genetically modified oncolytic adenovirus, which has been engineered to selectively infect cancer cells and activate the immune system. In June 2021, the 24-month follow-up in the malignant pleural mesothelioma (MPM) trial showed that median overall survival (mOS) for patients in first-line treatment with ONCOS-102 plus chemotherapy will be between 21.9 and 25.0 months, which is very encouraging in this patient population. For the first-line standard of care (SoC)-only control group mOS is 13.5 months, which is similar to outcomes from previously reported trials where patients received the same chemotherapy treatment. In this open label phase I/II trial, ONCOS-102 has been tested in first and second (or later) line MPM patients to assess safety, immune activation, and clinical efficacy of the combination of ONCOS-102 to SoC chemotherapy (pemetrexed/cisplatin).

Based on these encouraging pre-clinical and clinical effects associated with broad immune activation, the US FDA granted ONCOS-102 Fast Track designation for MPM in February 2021. Targovax has previously received orphan drug designation for MPM in both the US FDA and the European Medicines Agency.

On September 24, 2021 AstraZeneca and MSD reported that Positive high-level results from the PROpel Phase III trial showed it’s Lynparza (olaparib) in combination with abiraterone demonstrated a statistically significant and clinically meaningful improvement in radiographic progression-free survival (rPFS) versus standard-of-care abiraterone as a 1st-line treatment for men with metastatic castration-resistant prostate cancer (mCRPC) with or without homologous recombination repair (HRR) gene mutations (Press release, AstraZeneca, SEP 24, 2021, View Source [SID1234590249]).

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At a planned interim analysis, the Independent Data Monitoring Committee (IDMC) concluded that the trial met the primary endpoint of rPFS in men with mCRPC who had not received treatment in the 1st-line setting including with new hormonal agents (NHAs) or chemotherapy.

The trial also showed a trend at this interim analysis towards improved overall survival (OS). However, the data are still immature and the trial will continue to assess OS as a key secondary endpoint. The safety and tolerability were consistent with the known profiles of each medicine.

Prostate cancer is the second-most common cancer in men and despite an increase in the number of available treatments for men with mCRPC, five-year survival remains low.1

Susan Galbraith, Executive Vice President, Oncology R&D, said: "Today, men with metastatic castration-resistant prostate cancer have limited options in the 1st-line setting, and sadly often the disease progresses after initial treatment with current standards of care. These exciting results demonstrate the potential for Lynparza with abiraterone to become a new 1st-line option for patients regardless of their biomarker status and reach a broad population of patients living with this aggressive disease. We look forward to discussing the results with global health authorities as soon as possible."

Roy Baynes, Senior Vice President and Head of Global Clinical Development, Chief Medical Officer, MSD Research Laboratories, said: "We are encouraged by the PROpel results and the clinical benefit Lynparza in combination with abiraterone demonstrated versus abiraterone alone as a 1st-line treatment option for men with metastatic castration-resistant prostate cancer. Today’s results build on MSD and AstraZeneca’s commitment to bring Lynparza earlier in lines of treatment and to more patients with advanced prostate cancer."

The data will be presented at an upcoming medical meeting.

Metastatic castration-resistant prostate cancer
Metastatic prostate cancer is associated with a significant mortality rate.2 Development of prostate cancer is often driven by male sex hormones called androgens, including testosterone.3

In patients with mCRPC, their prostate cancer grows and spreads to other parts of the body despite the use of androgen-deprivation therapy to block the action of male sex hormones.3 Approximately 10-20% of men with advanced prostate cancer will develop CRPC within five years, and at least 84% of these men will have metastases at the time of CRPC diagnosis.4

Of men with no metastases at CRPC diagnosis, 33% are likely to develop metastases within two years.4 Despite advances in treatment for men with mCRPC, five-year survival is low and extending survival remains a key treatment goal.4

PROpel
PROpel is a randomised, double-blind, multi-centre Phase III trial testing the efficacy, safety, and tolerability of Lynparza versus placebo when given in addition to abiraterone in men with mCRPC who had not received prior chemotherapy or NHAs in the 1st-line setting. Men in both treatment groups will also receive either prednisone or prednisolone twice daily. The primary endpoint is rPFS and secondary endpoints include OS and time to first subsequent anticancer therapy or death.

The trial enrolled men with or without HRR gene mutations. They may have previously been treated with docetaxel at a prior stage of disease. The trial excluded men with prior treatment with abiraterone. Treatment with any other NHA must have been stopped one year or longer prior to randomisation.

Men must have had a performance status of 0-1 as defined by the Eastern Cooperative Oncology Group (ECOG) criteria and be a candidate for abiraterone treatment with documented evidence of progressive disease.

Preclinical trials in prostate cancer report a combined anti-tumour effect when PARP inhibitors and NHAs are administered together. PARP-1 is involved in the co-regulation of the androgen-receptor (AR) pathway, potentially leading to cooperation between PARP inhibitors and NHAs in blocking AR signalling.5

PARP inhibition plus androgen deprivation could significantly reduce the growth of prostate cancer cells independent of HRR gene status. Other trials revealed that treatment with NHAs inhibit the transcription of some HRR genes, therefore, inducing HRR deficiency and increased sensitivity to PARP inhibitors via non-genetic mechanisms. 6

Lynparza
Lynparza (olaparib) is a first-in-class PARP inhibitor and the first targeted treatment to block DNA damage response (DDR) in cells/tumours harbouring a deficiency in homologous recombination repair (HRR), such as those with mutations in BRCA1 and/or BRCA2, or those where deficiency is induced by other agents (such as NHAs).

Inhibition of PARP with Lynparza leads to the trapping of PARP bound to DNA single-strand breaks, stalling of replication forks, their collapse and the generation of DNA double-strand breaks and cancer cell death. Lynparza is being tested in a range of PARP-dependent tumour types with defects and dependencies in the DDR pathway.

Lynparza is currently approved in a number of countries, including those in the EU, for the maintenance treatment of platinum-sensitive relapsed ovarian cancer. It is approved in the US, the EU, Japan, China, and several other countries as 1st-line maintenance treatment of BRCA-mutated advanced ovarian cancer following response to platinum-based chemotherapy.

It is also approved in the US, EU and Japan as a 1st-line maintenance treatment with bevacizumab for patients with HRD-positive advanced ovarian cancer (BRCAm and/or genomic instability).

Lynparza is approved in the US, Japan, and a number of other countries for germline BRCA-mutated, HER2-negative, metastatic breast cancer, previously treated with chemotherapy; in the EU, this includes locally advanced breast cancer.

It is also approved in the US, the EU, Japan and several other countries for the treatment of germline BRCAm metastatic pancreatic cancer. Lynparza is approved in the US for HRR gene-mutated metastatic castration-resistant prostate cancer (BRCAm and other HRR gene mutations) and in the EU and Japan for BRCAm metastatic castration-resistant prostate cancer.

Regulatory reviews are underway in several countries for ovarian, breast, pancreatic and prostate cancers.

Lynparza, which is being jointly developed and commercialised by AstraZeneca and MSD, has been used to treat over 40,000 patients worldwide. Lynparza has the broadest and most advanced clinical trial development programme of any PARP inhibitor, and AstraZeneca and MSD are working together to understand how it may affect multiple PARP-dependent tumours as a monotherapy and in combination across multiple cancer types.

Lynparza is the foundation of AstraZeneca’s industry-leading portfolio of potential new medicines targeting DDR mechanisms in cancer cells.

The AstraZeneca and MSD strategic oncology collaboration
In July 2017, AstraZeneca and Merck & Co., Inc., Kenilworth, NJ, US, known as MSD outside the US and Canada, announced a global strategic oncology collaboration to co-develop and co-commercialise Lynparza, the world’s first PARP inhibitor, and Koselugo (selumetinib), a mitogen-activated protein kinase (MEK) inhibitor, for multiple cancer types.

Working together, the companies will develop Lynparza and Koselugo in combination with other potential new medicines and as monotherapies. Independently, the companies will develop Lynparza and Koselugo in combination with their respective PD-L1 and PD-1 medicines.

AstraZeneca in oncology
AstraZeneca is leading a revolution in oncology with the ambition to provide cures for cancer in every form, following the science to understand cancer and all its complexities to discover, develop and deliver life-changing medicines to patients.

The Company’s focus is on some of the most challenging cancers. It is through persistent innovation that AstraZeneca has built one of the most diverse portfolios and pipelines in the industry, with the potential to catalyse changes in the practice of medicine and transform the patient experience.

AstraZeneca has the vision to redefine cancer care and, one day, eliminate cancer as a cause of death.