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Y-mAbs Announces Update on DANYELZA® (naxitamab-gqgk) at ESMO

On December 9, 2020 Y-mAbs Therapeutics, Inc. (the "Company" or "Y-mAbs") (Nasdaq: YMAB) a commercial-stage biopharmaceutical company focused on the development and commercialization of novel, antibody-based therapeutic products for the treatment of cancer, reported that a clinical update on DANYELZA (naxitamab-gqgk) for the treatment of Refractory/Relapsed High-Risk Neuroblastoma was given at the ESMO (Free ESMO Whitepaper) Immuno-Oncology Virtual Congress 2020, which is being held December 9 through December 12, 2020 (Press release, Y-mAbs Therapeutics, DEC 9, 2020, View Source [SID1234572522]). The DANYELZA data was presented by Dr. Jaume Mora from SJD Barcelona Children’s Hospital, Spain and Dr. Daniel A. Morgenstern from The Hospital for Sick Children, Toronto, Canada.

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In the Company’s Study 201, a total of 95% of the infusions were administered in an outpatient setting. The median infusion time was 37 minutes, and all infusions were completed in less than 2 hours. The adherence rate was deemed very satisfactory, as 98% of the infusions were completed as planned, and the treatments appeared to be generally well tolerated. By independent review, the overall response rate ("ORR") in Study 201 was 68% with 59% complete responses ("CR"). In refractory patients, the ORR was 71% with 64% CR, and in relapsed patients the ORR was 63% with 50% CR.

DANYELZA 40mg/10ml was recently approved by the U.S. FDA. DANYELZA is indicated, in combination with granulocyte-macrophage colony-stimulating factor ("GM-CSF"), for the treatment of pediatric patients 1 year of age and older and adult patients with relapsed or refractory high-risk neuroblastoma in the bone or bone marrow who have demonstrated a partial response, minor response, or stable disease to prior therapy. DANYELZA is a humanized, monoclonal antibody that targets the ganglioside GD2, which is highly expressed in various neuroectoderm-derived tumors and sarcomas. During the Company’s Study 201, DANYELZA was primarily administered to patients in an outpatient setting three times in a week and the treatment was repeated every four weeks.

"I am very pleased to see that 98% of the infusions were completed as planned and 95% of the infusions were outpatient. Furthermore, the response rates achieved in these patients, who were either refractory to frontline treatment or had relapsed are notable, as this is a difficult to treat patient population, and the responses are based on antibody treatment alone, and not combination treatment with chemotherapy," said Thomas Gad, founder, Chairman and President.

"We are pleased that Study 201 showed that when DANYELZA is given in an outpatient setting with a high degree of treatment adherence, it addressed a significant unmet medical need in an efficient way. In addition, in Study 201 we saw that the median infusion time was just over half an hour, and when compared to the duration of the first infusion, the subsequent infusion times were generally lower, which we believe is great news for children living with refractory/relapsed high-risk neuroblastoma," said Dr. Claus Moller, Chief Executive Officer.

Researchers at Memorial Sloan Kettering Cancer Center ("MSK") developed DANYELZA, which is exclusively licensed by MSK to Y-mAbs. As a result of this licensing arrangement, MSK has institutional financial interests related to the compound and Y-mAbs.

About DANYELZA (naxitamab-gqgk)

DANYELZA (naxitamab-gqgk) is indicated, in combination with granulocyte-macrophage colony-stimulating factor ("GM-CSF"), for the treatment of pediatric patients 1 year of age and older and adult patients with relapsed or refractory high-risk neuroblastoma in the bone or bone marrow who have demonstrated a partial response, minor response, or stable disease to prior therapy. This indication was approved under accelerated approval based on overall response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefits in a confirmatory trial. DANYELZA includes a Boxed Warning for serious infusion-related reactions, such as cardiac arrest, anaphylaxis, hypotension, bronchospasm and stridor and neurotoxicity, such as severe neuropathic pain, transverse myelitis and reversible posterior leukoencephalopathy syndrome. See full Prescribing Information for complete Boxed Warning and other important safety information.

Full data set of Oncopeptides phase 2 HORIZON study in multiple myeloma published in the Journal of Clinical Oncology

On December 9, 2020 Oncopeptides AB (publ) (Nasdaq Stockholm: ONCO), a pharmaceutical company focused on the development of targeted therapies for difficult-to-treat hematological diseases, reported that the pivotal phase 2 HORIZON study evaluating intravenous melflufen (INN melphalan flufenamide) in combination with dexamethasone in relapsed refractory multiple myeloma, has been published in the peer-reviewed Journal of Clinical Oncology (Press release, Oncopeptides, DEC 9, 2020, View Source [SID1234572521]).

The phase 2 HORIZON data are the basis for the ongoing priority review of the New Drug Application to the US Food and Drug Administration FDA, for accelerated approval of melflufen in combination with dexamethasone in triple-class refractory multiple myeloma patients, who are refractory to at least one proteasome inhibitor, one immunomodulatory drug and one anti-CD38 monoclonal antibody.

"The results from the HORIZON study demonstrate that melflufen in combination with dexamethasone, has a potential to provide a therapeutic option for patients who are difficult to treat and have a poor prognosis, including patients with triple class refractory myeloma and patients with extramedullary disease", says Klaas Bakker, MD, PhD, Chief Medical Officer, Oncopeptides AB. "These patients have limited, or no treatment options left. The introduction of a new treatment class may represent a potentially important alternative".

The phase 2 HORIZON study is a pivotal, single-arm, multicenter, phase 2 study evaluating the safety and efficacy of melflufen in combination with dexamethasone in patients with relapsed refractory multiple myeloma. The study included 157 heavily pretreated patients, who had received >2 earlier lines of therapy with immunomodulatory drugs and proteasome inhibitors and were refractory to pomalidomide and/or daratumumab. The HORIZON study population includes subgroups of patients who were triple?class refractory and/or had extramedullary disease and/or had cytogenetic high?risk features.

Summary of results:

30 Intention to Treat (n=157) Triple Class Refractory (n=119) Extra Medullary Disease (n=55)
Overall Response Rate (ORR) 29% 26% 24%
Median Progression Free Survival (PFS)) 4.2 months 3.9 months 2.9 months
Median Overall Survival (OS) 11.6 months 11.2 months 6.5 months
Responding patients n=45 n=31 n=13
Median Duration of Response (DOR) 5.5 months 4.4 months 5.5 months
Median Progression Free Survival (PFS) 8.5 months 8.5 months 17.3 months
The publication is available on; View Source

The information in this press release was submitted for publication on December 9, 2020 at 22:00 (CET).

About melflufen
Melflufen (INN melphalan flufenamide) is a first in class peptide-drug conjugate (PDC) that targets aminopeptidases and rapidly releases alkylating agents into tumor cells. Melflufen is rapidly taken up by myeloma cells due to its high lipophilicity and is immediately hydrolyzed by peptidases to release an entrapped hydrophilic alkylator payload. Aminopeptidases are overexpressed in tumor cells and are even more pronounced in advanced cancers and tumors with a high mutational burden. In vitro, melflufen is 50-fold more potent in myeloma cells than the alkylator payload itself due to the increased intracellular alkylator concentration. Melflufen displays cytotoxic activity against myeloma cell lines resistant to other treatments, including alkylators, and has also demonstrated inhibition of DNA repair induction and angiogenesis in preclinical studies. In the pivotal phase 2 HORIZON study melflufen plus dexamethasone demonstrated encouraging efficacy and a clinically manageable safety profile in heavily pretreated patients with relapsed refractory multiple myeloma, with primarily hematologic Adverse Events (AE) and a low incidence of non-hematologic AEs.

Cancer Detection using BioChain’s cfPure kit

On December 9, 2020 Biochain reported that There have been tremendous advances in cancer treatment since President Richard Nixon declared war on malignancies in 1971 (Press release, Biochain, DEC 9, 2020, View Source [SID1234572520]). Despite having treatments such as targeted radiation, estrogen blockers, and CAR-T cell immunotherapies, early detection of cancer remains one of the most important factors. For instance, the five-year relative survival rate for non-small cell lung cancer is 61% when cancer has not yet spread outside the lung. The survival rate drops to 35% once the cancer invades nearby structures, and to 6% once it metastasizes to other organ systems.

However, early detection of cancer has proven easier said than done, and not without risks. When screening for cancer certain number of patients experience anxiety and undergo unnecessary invasive procedures based on false positives. While some cancers make for relatively easy screening such as cervical cancer via the Pap test, many cancers are inaccessible, and tissue biopsy too invasive for population-level screenings.

The oncologist’s objective is to come up with a less invasive way of screening the healthy population for specific and accurate indications of early-stage cancer. This motivated scientists to develop "liquid biopsy," where doctors hope to detect tumor-specific protein biomarkers or cancer-associated genetic mutations in circulating free DNA (cfDNA) blood samples.

In an article published in the journal Science, Johns Hopkins researchers Bert Vogelstein and Nickolas Papadopoulos and their colleagues appear to have done exactly that.

A leap in early cancer detection

A breakthrough was achieved using a liquid biopsy test called "DETECT-A" ̶̶ Detecting cancers Earlier Through Elective mutation-based blood Collection and Testing ̶ which involved more than 9,911 women who had no history of cancer. The study used a multi-cancer blood test, to identify 26 undiagnosed cancers in 10 different organ systems: appendix, breast, colorectal, kidney, lung, lymphomas, ovary, thyroid, uterine and unknown primary site. The tumors were then localized using techniques such as PET-CT, a combination that was 99.6% specific.

Importantly, 17 of the cancers detected by the blood test were diagnosed at an early stage. Twelve of the 26 patients were in remission and eight were still in treatment or had stable disease nine months post-diagnosis.

This was a landmark result for the liquid biopsy field and the industry took note. A more advanced version of the multi-cancer blood test known as CancerSEEK had been licensed by Johns Hopkins to Thrive Earlier Detection Corp for development. On Oct. 27, Exact Sciences announced it would acquire Thrive for $2.15 billion.

Foundational technology

Although much of the liquid biopsy breakthrough has come from next-generation sequencing (NGS) and machine learning, the fundamentals of the field are still focused on an accurate and successful sampling process. If there is no adequate sample in the first place, no algorithm can support it. The DETECT-A study made use of the cfPure extraction kit from BioChain, a magnetic bead-based technology that demonstrated high yields in extracting cfDNA from blood plasma. "In order to get that cfDNA, you need to have the right tools," says BioChain’s Production and R&D Manager Dr. Franklin Chin, "and we have them. Our extraction kit is the first step in any research that involves cfDNA biomarker discovery"

The cfPure kits are available from BioChain in three different sizes for the extraction of a maximum of 250 ml of cfDNA from human plasma samples. The kit has two different versions: the original cfPure kit which maximizes yield, and the "V2," which minimizes carryover of genomic DNA into the final elution.

Dr. Bert Vogelstein and his colleagues used the original version of cfPure kits, and the fact that such pioneering researchers used BioChain’s technology in a groundbreaking study to process tens of thousands of samples is a source of pride for BioChain. "Dr. Vogelstein is one of the pioneers of liquid biopsy research," Chin says, "that he is using our kit is pretty big for us."

Detection of early-stage cancer using the DETECT-A test is just the first of many breakthroughs BioChain hopes their technology will enable. Beyond early diagnosis, for instance, there are efforts at precision tumor treatment and companion diagnostics, according to Chin. Many cancers are drug-resistant, and that resistance is based on their mutational profile. Pairing the cfPure kit with NGS using specific biomarker panels can help identify the mutational landscape for a patient, indicating the therapies best suited to treating their specific cancer.

Chin also hopes to see BioChain’s technology used in the creation of biomarker panels to help identify mutations with a strong correlation to oncogenesis. "You need to have a solid foundation," he says. "You need to collect as many samples as possible, analyze them, and come up with a panel of biomarkers." That will expand the reach and accuracy of liquid biopsy, and, ultimately, the success of cancer treatments. That’s something Chin and BioChain are excited to be a part of.

A menu of research solutions

Whatever your research needs, BioChain offers a cfPure cell-free DNA extraction kit providing market-leading yields for the best possible input for NGS or other processing.

BioChain also offers blood plasma and tissue samples for researchers who need inputs to develop and test their technologies and offers the cfPure cell-free DNA extraction process as a service for those who cannot perform the extractions themselves.

Oncolytics and SOLTI Report Clinical Synergy of Pelareorep with Checkpoint Inhibitors at the 2020 San Antonio Breast Cancer Symposium

On December 9, 2020 Oncolytics Biotech Inc. (NASDAQ: ONCY) (TSX: ONC) and SOLTI-Innovative Breast Cancer Research reported an electronic poster at the 2020 San Antonio Breast Cancer Symposium (SABCS) with data from the AWARE-1 window-of-opportunity study in patients with early-stage breast cancer showing pelareorep delivers a significant boost known to increase the effectiveness of checkpoint inhibitors (Press release, Oncolytics Biotech, DEC 9, 2020, View Source [SID1234572519]).

In the AWARE-1 study, a collaboration between Oncolytics Biotech and SOLTI, early-stage breast cancer patients are treated with pelareorep, with or without atezolizumab (Tecentriq), plus an appropriate therapy for each patient’s breast cancer subtype, followed by surgery. The SABCS poster includes 17 out of the 20 HR+/HER2- breast cancer patients comprising the study’s first two cohorts, the targeted patient population for our intended phase 3 study. Treatment with pelareorep increased the CelTIL score in tumor biopsies, which has been associated with improved clinical outcomes. In addition, pelareorep treatment dramatically upregulated PD-L1 expression in the tumor microenvironment (TME). These findings highlight the potential of pelareorep to act synergistically with checkpoint inhibitors and also provides a basis for the near doubling of overall survival observed in a prior phase 2 trial when pelareorep was added to chemotherapy in HR+/HER2- breast cancer patients (link to PR, link to poster).

"AWARE-1 data demonstrate pelareorep’s consistent remodeling of the tumor immune environment," said Dr. Aleix Prat, M.D., Ph.D., Translational Investigator of AWARE-1, SOLTI President and Head of the Medical Oncology Department at Hospital Clinic in Barcelona. "Pelareorep seems to train the immune system to target cancer cells while simultaneously promoting tumor inflammation and priming a response to immune checkpoint blockade. This demonstrates pelareorep’s potential to overcome the immunosuppressive nature of the tumor microenvironment which could limit checkpoint inhibitor efficacy."

Key data and conclusions from the SABCS poster include:

72% of evaluated patients (n=18) saw an increase in CelTIL, the study’s primary endpoint that is associated with favorable clinical outcomes.
The maximum percentage increase in CelTIL (~300%) was achieved in a cohort 2 patient receiving pelareorep in combination with checkpoint blockade therapy.
On average, there was a 105-fold increase in TME PD-L1 expression (n=13) from baseline (pre-pelareorep administration) to surgery (21-days post-administration).
Tumor microenvironment PD-L1 expression increased in all evaluated patients (n=13).
Preliminary imaging mass cytometry analysis showed pelareorep treatment promoted broad anti-tumor changes in the TME, including enhanced CD8+ T cell activation and the recruitment of memory T cells.
Thomas Heineman, M.D., Ph.D., Global Head of Clinical Development and Operations at Oncolytics, commented, "In the AWARE-1 study, pelareorep delivered consistent increases in tumor PD-L1 expression and recruitment of anti-cancer immune cells into tumors, as well as increases in CelTIL score for over 70% of the patients. This is highly encouraging given the association between CelTIL and clinical outcomes, and we hope to observe the same success from our phase 2 BRACELET-1 trial, which is exclusively enrolling HR+/HER2- breast cancer patients."

Andrew de Guttadauro, President of Oncolytics Biotech U.S. and Global Head of Business Development, added, "Immune deserts or immunosuppressive tumor microenvironments limit tumor PD-L1 expression levels and thereby limit regulatory approval and commercial success of checkpoint inhibitors in certain breast and other malignancies. AWARE-1 data show that pelareorep can alter the tumor microenvironment and induce robust PD-L1 expression, highlighting the potential of pelareorep to boost the efficacy of checkpoint inhibitors and increase the proportion of patients eligible for these therapies. We expect this synergistic potential to enable the continued execution of our strategy to develop pelareorep-based therapies in collaboration with industry leaders."

The electronic poster, titled "A window-of-opportunity study with atezolizumab and the oncolytic virus pelareorep in early breast cancer (REO-027, AWARE-1)" is available in the SABCS virtual poster hall and on the Posters & Publications page of Oncolytics’ website (LINK).

Ongoing ‘trial-in-progress’ posters giving an overview of Oncolytics’ IRENE and BRACELET-1 study designs were also presented at SABCS and are available at the same locations.

About AWARE-1

AWARE-1 is an open-label window-of-opportunity study in early-stage breast cancer enrolling 38 patients into five cohorts:

Cohort 1 (n=10), HR+ / HER2- (pelareorep + letrozole)
Cohort 2 (n=10), HR+ / HER2- (pelareorep + letrozole + atezolizumab)
Cohort 3 (n=6), TNBC (pelareorep + atezolizumab)
Cohort 4 (n=6), HR+ / HER2+ (pelareorep + trastuzumab + atezolizumab)
Cohort 5 (n=6), HR- / HER2+ (pelareorep + trastuzumab + atezolizumab)
The study combines pelareorep, with or without atezolizumab, and the standard of care therapy according to breast cancer subtype. Patients are biopsied as part of their initial breast cancer evaluation, then again on day three following initial treatment, and a final tissue sample after three weeks, on the day of their mastectomy. Data generated from this study are intended to confirm that the virus is acting as a novel immunotherapy and to provide comprehensive biomarker data by breast cancer subtype. The primary endpoint of the study is overall CelTIL (a measurement of cellularity and tumor-infiltrating lymphocytes). Secondary endpoints for the study include CelTIL by breast cancer subtype, safety, and tumor and blood-based biomarkers.

For more information about the AWARE-1 study, refer to View Source

Tecentriq (atezolizumab) is a registered trademark of Genentech, a member of the Roche Group.

About Breast Cancer

Breast cancer is the most common cancer in women worldwide, with over two million new cases diagnosed in 2018, representing about 25 percent of all cancers in women. Incidence rates vary widely across the world, from 27 per 100,000 in Middle Africa and Eastern Asia to 85 per 100,000 in Northern America. It is the fifth most common cause of death from cancer in women globally, with an estimated 522,000 deaths.

Breast cancer starts when cells in the breast begin to grow out of control. These cells usually form a tumor that can often be seen on an x-ray or felt as a lump. The malignant tumor (cancer) is getting worse when the cells grow into (invade) surrounding tissues or spread (metastasize) to distant areas of the body.

About Pelareorep

Pelareorep is a non-pathogenic, proprietary isolate of the unmodified reovirus: a first-in-class intravenously delivered immuno-oncolytic virus for the treatment of solid tumors and hematological malignancies. The compound induces selective tumor lysis and promotes an inflamed tumor phenotype through innate and adaptive immune responses to treat a variety of cancers and has been demonstrated to be able to escape neutralizing antibodies found in patients.

Curis Announces Pricing of Public Offering of Common Stock

On December 9, 2020 Curis, Inc. (NASDAQ:CRIS), a biotechnology company focused on the development of innovative therapeutics for the treatment of cancer, reported the pricing of an underwritten public offering of 25,652,174 shares of its common stock at a public offering price of $5.75 per share for total gross proceeds of approximately $147.5 million (the "Offering") (Press release, Curis, DEC 9, 2020, View Source [SID1234572518]). Curis has granted the underwriters a 30-day option to purchase up to an additional 3,847,826 shares of common stock on the same terms and conditions. The Offering is expected to close on or about December 11, 2020, subject to customary closing conditions.

Cantor Fitzgerald & Co. and JonesTrading Institutional Services LLC are acting as joint book-runners for the Offering. H.C. Wainwright & Co., LLC and Laidlaw & Company (UK) Ltd. are acting as co-lead managers for the Offering.

Curis intends to use the net proceeds from the Offering, together with its existing cash and cash equivalents, to continue development of CA-4948, in collaboration with Aurigene, and CI-8893, in collaboration with ImmuNext, and for general working capital and capital expenditures.

The securities in the Offering are being offered pursuant to a shelf registration statement on Form S-3 (File No. 333-224627) that was filed with the United States Securities and Exchange Commission ("SEC") on May 3, 2018, and declared effective by the SEC on May 17, 2018 and an additional registration statement on Form S-3 (File No. 333-224627) filed pursuant to Rule 462(b) which became automatically effective on December 9, 2020. A final prospectus supplement and accompanying prospectus relating to the Offering will be filed with the SEC and will be available on the SEC’s website at www.sec.gov. Copies of the final prospectus supplement and the accompanying prospectus, when available, may also be obtained by contacting Cantor Fitzgerald & Co., Attention: Capital Markets, 499 Park Ave., 6th Floor, New York, New York 10022 or by email at [email protected].

The securities described above have not been qualified under any state blue sky laws. This press release shall not constitute an offer to sell or the solicitation of an offer to buy these securities, nor shall there be any sale of these securities in any state or other jurisdiction in which such offer, solicitation or sale would be unlawful prior to the registration or qualification under the securities laws of any such state or other jurisdiction.