On May 29, 2020 ALX Oncology Holdings Inc., a clinical-stage immuno-oncology company developing therapies that block the CD47 checkpoint pathway, reported the final results from the fully enrolled ALX148 plus pembrolizumab and ALX148 plus trastuzumab portions of the Phase 1 clinical program at the 2020 ASCO (Free ASCO Whitepaper) Annual Meeting [Abstract #3056] (Press release, ALX Oncology, MAY 29, 2020, View Source [SID1234558723]). In addition, preliminary data were presented from patients administered ALX148 plus standard chemotherapy-containing regimens.

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!

As of April 01, 2020, eighty-nine patients with advanced solid tumors were administered ALX148 in combination with standard regimens of: 1) pembrolizumab, 2) trastuzumab, 3) pembrolizumab plus 5-fluorouracil plus platin, or 4) trastuzumab plus ramucirumab plus paclitaxel. Expansion cohorts comprising patients with previously treated advanced squamous cell carcinoma of the head and neck (HNSCC) and advanced gastric/gastroesophageal junction cancer (G/GEJ) demonstrated objective responses with the following key results in response-evaluable patients:

ALX148 plus pembrolizumab (n=20): Subjects with advanced HNSCC whose tumors had progressed on standard first-line therapy demonstrated an objective response rate (ORR) of 20% and a disease control rate of 30%.
– Subjects with advanced HNSCC who had never received prior checkpoint inhibitor therapy (n=10) demonstrated an ORR of 40%, median progression-free survival (PFS) of 4.61 months, and median overall survival (OS) that was not reached with a median follow-up of 17.9 months.

ALX148 plus trastuzumab (n=19): Subjects with advanced HER2 positive G/GEJ whose tumors had progressed on standard first-line therapy, including trastuzumab, demonstrated an ORR of 21%, median PFS of 2.17 months, and median OS of 11.5 months.
ALX148 displayed a favorable safety profile with no exposure-dependent cytopenia observed across the dose range evaluated. Preliminary data suggest that ALX148 can be combined with chemotherapy-containing regimens with objective responses observed in patients with HNSCC and G/GEJ disease.

"We believe the compelling clinical activity and tolerability observed with ALX148 in combination with a variety of anti-cancer antibodies and a checkpoint inhibitor suggests that ALX148 has the potential to become a cornerstone therapy for the treatment of patients with cancer," said Sophia Randolph, M.D., Ph.D., Chief Medical Officer of ALX Oncology. "Notably, the initial safety profile of ALX148 in combination with chemotherapy may support broad therapeutic potential for ALX148 in patients in need of novel chemotherapy-based therapies early in the course of their disease."

On May 29, 2020 Marker Therapeutics, Inc. (Nasdaq:MRKR), a clinical-stage immuno-oncology company specializing in the development of next-generation T cell-based immunotherapies for the treatment of hematological malignancies and solid tumor indications, reported updated clinical results from an ongoing investigator-sponsored Phase 1 trial led by the Baylor College of Medicine, evaluating the Company’s MultiTAA-specific T cell therapy in patients with advanced or metastatic pancreatic adenocarcinoma (Press release, TapImmune, MAY 29, 2020, View Source [SID1234558739]). Data from a cohort of patients receiving MultiTAA-specific T cell therapy in combination with standard-of-care chemotherapy in the first-line setting (Arm A), were reviewed today by lead investigator, Brandon G. Smaglo, M.D., FACP, as part of a poster session during the 2020 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Virtual Annual Meeting. ASCO (Free ASCO Whitepaper) is being held from Friday, May 29 through Sunday, May 31, 2020.

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!

"Pancreatic cancer is one of the most deadly forms of cancer today, with the mortality rate remaining relatively unchanged over the past several decades despite ongoing research and treatment advances," said Dr. Brandon G. Smaglo. "With a growing body of data, we continue to be encouraged by the potential of MultiTAA-specific T cell therapy, in combination with standard-of-care chemotherapy, to safely produce durable responses in patients with advanced pancreatic cancer. In this study, a number of patient responses occurred after the period in which a chemotherapy-driven response would typically occur, suggesting MultiTAA’s potential to produce added benefit in this patient population. Additionally, we also observed induction of the endogenous immune system – or epitope spreading – suggesting that the benefits of MultiTAA may extend beyond the targeted antigens and further contribute to a long-lasting anti-tumor effect."

Presentation Title:

"A phase I trial targeting advanced or metastatic pancreatic cancer using a combination of standard chemotherapy and adoptively transferred nonengineered, multiantigen specific T cells in the first-line setting (TACTOPS)"

Study Design:

Arm A is evaluating the safety and potential efficacy of using MultiTAA-specific T cells in the first-line setting for chemo-responsive patients with pancreatic adenocarcinoma. Patients in Arm A receive at least three months of standard-of-care chemotherapy (gemcitabine/nab-paclitaxel or FOLFIRINOX) – the period during which a response to chemotherapy would typically occur – before receiving up to six administrations of MultiTAA-specific T cells in conjunction with chemotherapy.

Summary of Interim Results

Between June 2018 and December 2019, 13 patients have been treated, each of whom received up to 6 monthly infusions of 1×107 MultiTAA-specific T cells/m2 in conjunction with ongoing first-line chemotherapy and without prior protocol-associated lymphodepletion. For 12 of the 13 patients, sufficient cells for all six planned doses were generated; two doses were available for the remaining patient.

·Out of the 13 evaluable patients (best overall response):

o4 patients experienced objective responses after administration of MultiTAA cells;

§1 patient experienced a radiographic complete response occurring at month 9 after starting chemotherapy;

§3 patients experienced partial responses per RECIST occurring at 6-9 months after starting chemotherapy;

o6 patients experienced stable disease;

o1 patient experienced a mixed response (some lesions increased in size and others decreased for a net zero change in size of tumor lesions);

o2 patients experienced disease progression;

·For 9 of the 13 patients, the cancer was controlled for a period longer than historical controls relative to the type of chemotherapy used
·5 patients enrolled in the study were not administered MultiTAA-specific T cells, either because of disease progression (4 patients) which made them ineligible for treatment, or because insufficient starting material from the patient was available for manufacturing (1 patient);
·Evidence of epitope-spreading was observed in all responders, suggesting that the MultiTAA T cell therapy triggered the recruitment of a broader endogenous immune system response for improved anti-tumor activity;
·No infusion-related reactions, cytokine release syndrome or neurotoxicity was observed.

Mythili Koneru, M.D., Ph.D., Chief Medical Officer of Marker Therapeutics commented: "We are pleased with these interim results, which demonstrate the potential of our therapy to simultaneously recognize and target multiple antigens. As the tumor microenvironment varies from patient to patient, the ability to address these differences may offer a significant benefit to patients. While these results represent a small patient population, we look forward to generating additional data that may support MultiTAA’s future development in this challenging disease area."

The TACTOPS poster and corresponding recorded presentation by Dr. Smaglo will be available on demand through the ASCO (Free ASCO Whitepaper)20 Virtual Scientific Program on the ASCO (Free ASCO Whitepaper) website beginning on May 29, 2020, at 8:00 a.m. EDT.

Conference Call and Webcast
Marker will host a conference call and webcast on Monday, June 1st at 8:00 am EDT featuring Dr. Brandon Smaglo, as well as Marker senior management, to discuss the data. The webcast will be accessible in the Investors section of the Company’s website at markertherapeutics.com. Individuals can participate in the conference call by dialing 877-407-8913 (domestic) or 201-689-8201 (international).

The archived webcast will be available for replay on the Marker website following the event.

About MultiTAA-Specific T Cell Therapy

Marker’s Multi-Antigen Targeted (MultiTAA) platform is a novel, non-genetically modified cell therapy approach that selectively expands tumor-specific T cells from a patient’s blood capable of recognizing a broad range of tumor antigens. In early clinical trials, the multi-antigen approach has been well tolerated and shown to enhance tumor destroying capability and is one of the first therapies to consistently demonstrate epitope spreading – inducing the patient’s own T cells to expand, potentially contributing to a lasting anti-tumor effect. Unlike other cell therapies which require pre-conditioning regimens and hospitalization, MultiTAA is designed to be administered in an outpatient setting.

On May 29, 2020 Regeneron Pharmaceuticals, Inc. (NASDAQ: REGN) reported that it has completed the secondary offering of 13,014,646 shares of its common stock held by Sanofi, which includes the exercise in full of the underwriters’ option to purchase additional shares from Sanofi, at a public offering price of $515.00 per share (Press release, Regeneron, MAY 29, 2020, View Source [SID1234558757]). The Company also announced the completion of its repurchase of 9,806,805 shares directly from Sanofi at a price of $509.85 per share (representing the price paid by the underwriters in the offering), for an aggregate purchase amount of $5 billion. Pursuant to the offering and repurchase, Sanofi has disposed of all of its shares of common stock in Regeneron, other than 400,000 shares that it is retaining.

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!

Regeneron did not receive any of the proceeds from the sale of shares of its common stock by Sanofi. The public offering occurred simultaneously in the United States and internationally through underwriters led by BofA Securities and Goldman Sachs & Co. LLC, together with Barclays, BNP Paribas, Citigroup, J.P. Morgan, Morgan Stanley as joint book-running managers.

Regeneron has filed a registration statement (including a prospectus) with the SEC for the offering. Before you invest, you should read the prospectus in that registration statement and other documents Regeneron has filed and will file with the SEC, including the final prospectus supplement dated May 26, 2020, for more complete information about Regeneron and this offering. You may get these documents for free by visiting EDGAR on the SEC website at www.sec.gov. Alternatively, any underwriter or any dealer participating in the offering will arrange to send you the prospectus and the prospectus supplement, if you request them by contacting BofA Securities, NC1-004-03-43, 200 North College Street, 3rd Floor, Charlotte, NC 28255-0001, Attention: Prospectus Department or by email at [email protected]; or Goldman Sachs & Co. LLC, Attention: Prospectus Department, 200 West Street, New York, New York 10282, via telephone: 1-866-471-2526, or via email: [email protected].

On May 29, 2020 The University of Texas MD Anderson Cancer Center reported that results from a Phase I clinical trial led by researchers the adoptive T-cell therapy ADP-A2M4, which is engineered to express a T-cell receptor (TCR) directed against the MAGE-A4 cancer antigen, achieved responses in patients with multiple solid tumor types, including #102synovial sarcoma, head and neck cancer and lung cancer (Press release, MD Anderson, MAY 29, 2020, View Source [SID1234558773]).

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!

Among 38 patients treated on the trial, the ADP-A2M4 T cells resulted in overall response (OR), or tumor shrinkage, in 9 patients (23.7%) and stable disease in 18 patients (47.4%). Trial data were shared in an oral presentation at the 2020 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting by principal investigator David Hong, M.D., professor of Investigational Cancer Therapeutics.

"Thus far, we haven’t seen strong responses in treating solid tumors with available cellular therapies, in large part because antigens expressed are not restricted to the tumors," said Hong. "In this trial, I’ve been encouraged to see durable responses in several patients, and the results suggest there is potential for this emerging TCR-based technology for treating solid tumors."

Adoptive cellular therapy is a form of immunotherapy that modifies immune cells to be more effective in mounting an immune response against cancer. For ADP-A2M4, T cells are isolated from patients and engineered to express a TCR targeting MAGE-A4, a protein normally expressed only in the testis but present in certain cancers.

Unlike chimeric antigen receptor (CAR)-modified T cells, which target surface proteins on cancer cells, TCR T-cell therapies are able to target proteins normally found inside the cell by recognizing protein fragments bound to immune-related proteins on the cell surface.

The Phase I trial was designed as a dose-escalation study to assess the safety, tolerability and antitumor activity of ADP-A2M4 in patients with advanced solid tumors with expression of the MAGE-A4 protein. Patients on the trial included those with synovial sarcoma, ovarian cancer, head and neck cancer, gastric cancer, myxoid/round cell liposarcoma, non-small cell lung cancer, bladder cancer, esophageal cancer and melanoma. Participants had a median of three prior lines of systemic therapy.

The therapy achieved strong responses in particular groups of patients in the trial. Patients with synovial sarcoma saw a 43.8% OR rate and a disease control rate of more than 90%. There also was an additional patient with an unconfirmed response after the data cut-off. Median duration of response in these patients was 28 weeks and median progression-free survival was 20 weeks. Confirmed responses were also seen in patients with lung cancer and head and neck cancer.

Most patients (97.4%) experienced some treatment-related adverse events, with the most common being low blood cell counts (lymphopenia, leukopenia, neutropenia, anemia and thrombocytopenia). Half of patients experienced cytokine release syndrome. Two patients had trial-related deaths, which led to modification of the lymphodepletion regimen and eligibility criteria.

"The side effects seen on the trial were largely consistent with those typically experienced by cancer patients undergoing lymphodepleting chemotherapy and cellular therapy," said Hong. "This study is a nice proof of concept for treating solid tumors and suggests there could be a role for cellular therapies in these indications going forward."

This research is part of an ongoing strategic alliance between MD Anderson and Adaptimmune, designed to expedite the development of novel T-cell therapies for multiple cancer types. Translational research and analyses of related biomarkers continues. Results from this study led to a low-dose radiation sub-study, a Phase II trial of ADP-A2M4 in sarcoma and a Phase I trial of Adaptimmune’s next-generation T-cell therapy targeting MAGE-A4, ADP-A2M4CD8.

On May 29, 2020 Achilles Therapeutics ("Achilles"), a clinical stage biopharmaceutical company developing personalised cancer immunotherapies, reported that it has dosed the first patient in a Phase I/II study of a clonal neoantigen T cell (cNeT) therapy in patients with recurrent or metastatic malignant melanoma (Press release, Achilles Therapeutics, MAY 29, 2020, View Source [SID1234558656]). This is the first tumour-infiltrating lymphocyte (TIL) therapy to enter clinical trials where the TILs have been specifically selected to target clonal neoantigens – antigens which are believed to be present on all tumour cells.

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 THETIS study is an open-label, multi-centre Phase I/II trial evaluating the safety, tolerability and clinical efficacy of cNeT therapy as a single dose in patients with recurrent or metastatic malignant melanoma. The trial is expected to recruit approximately 20 patients and report initial data in the first half of 2021. Recruitment is ongoing across sites in the UK, with additional sites to open in the US and Europe. Link to Study.

"The dosing of our first melanoma patient with a cell therapy to specifically target all cancer cells, marks a significant milestone in delivering the first precision TIL therapy. We have used a unique and proprietary data set derived from cancer patients over a period of many years (TRACERx) to generate a powerful predictive tool which, together with the DNA of a patient’s own tumour, can be used to create an entirely personalised cell therapy designed to be exquisitely specific and effective," said Dr Iraj Ali, CEO of Achilles Therapeutics. "As we continue to navigate the unprecedented COVID-19 pandemic, we are incredibly grateful to patients and their families, investigators and their colleagues at clinical study sites, and our employees for working to advance this important study that has the potential to treat a very challenging and life-threatening cancer."

"Patients with metastatic melanoma have very limited treatment options after immune checkpoint inhibitors have failed," said Professor Ruth Plummer, Clinical Professor of Experimental Cancer Medicine, Faculty of Medical Sciences, Newcastle University and The Newcastle upon Tyne Hospitals NHS Foundation. "This is the first patient in the UK to receive a personalised clonal neoantigen reactive T cell product and we are very excited that this has been achieved in Newcastle in the midst of such unprecedented times, and is testament to the great collaboration between us and Achilles."

Achilles is developing personalised T cell therapies for solid tumours targeting clonal neoantigens: protein markers unique to each patient that are present on the surface of all cancer cells. Using its PELEUS bioinformatics platform, Achilles can identify clonal neoantigens from each patient’s unique tumour profile which are present on every cancer cell. Achilles uses its proprietary process to manufacture T cells (cNeT) which exquisitely target a specific set of clonal neoantigens in each patient. Targeting multiple clonal neoantigens that are present on all cancer cells, but not on healthy cells, reduces the risk that new mutations can induce immune evasion and therapeutic resistance, and allows individualised treatments to target and destroy tumours without harming healthy tissue.