On November 30, 2021 Neuramedy reported that NM-101 (tomaralimab), a monoclonal antibody against TLR-2 Alpha-synucleinopathies are neurodegenerative diseases caused by the abnormal accumulation of misfolded alpha-synuclein in neurons and glial cells (Press release, Neuramedy, NOV 30, 2021, View Source [SID1234632172]). There are three major types of alpha-synucleinopathies: Parkinson’s disease (PD), dementia with Lewy bodies (DLB), and multiple system atrophy (MSA).

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Misfolded alpha-synucleins can promote neuroinflammation and neuronal loss and also spread to the neighboring neurons, which are mediated by Toll-like Receptor-2 (TLR-2). Furthermore, TLR-2 is found to be up-regulated in alpha-synucleinopathies.

Therefore, the inhibition of TLR-2 would be one of the promising therapeutic strategies to slow down or halt the progression of alpha-synucleinopathies, along with the therapies targeting alpha-synuclein.

Neuramedy, headquartered in Seoul, is a biotech company focusing on novel therapeutic approaches to treat alpha-synucleinopathies, based on the findings above.

Neuramedy’s NM-101 (tomaralimab) is a first-in-class humanized IgG4 monoclonal antibody against TLR-2 which was originally developed and termed ‘OPN-305’ by Opsona Therapeutics (Dublin, Ireland) for the treatment of myelodysplastic syndrome in 2015. Neuramedy took over the patent and global rights for tomaralimab from Opsona in 2019 and is now applying it to PD.

The company is expanding the potential application of tomaralimab to the treatment of Alzheimer’s disease (AD) in conjunction with Amyloid Solution (Seongnam, South Korea) under the name of ‘AS-M801’, considering that TLR-2 is also up-regulated in beta-amyloidopathy like AD and activated by beta-amyloid as in PD and by alpha-synuclein.

Neuramedy is also developing its novel BBB-penetrating antibody (NM-301) for the treatment of neurodegenerative diseases, in collaboration with Aptamer Sciences, a front-runner in Aptamer Technology that will provide antibodies with a BBB shuttle.

In parallel with these, the company is additionally developing its innovative small molecules (NM-401, NM-402, and NM-403) that can inhibit the aggregation of alpha-synucleins for the treatment of various alpha-synucleinopathies (PD, MSA, and DLB), conjointly with Yungjin Pharm.

Neuramedy is planning to initiate its phase 1b/2a clinical trials of NM-101 for the treatment of AD in the U.S. next year.

On November 30, 2021 IMV Inc. (NASDAQ: IMV; TSX: IMV), a clinical-stage company developing a portfolio of immune-educating therapies based on its novel DPX platform to treat solid and blood cancers while preserving patients’ quality of life, reported that the first patient with hormone receptor positive/HER2-negative (HR+/HER2-) breast cancer has been dosed with its lead compound, maveropepimut-S (MVP-S, formerly known as DPX-Survivac) (Press release, IMV, NOV 30, 2021, View Source [SID1234596257]). In this trial, MVP-S is being administered in combination with an aromatase inhibitor, with or without radiotherapy or cyclophosphamide prior to surgery.

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"We are excited to see maveropepimut-S evaluated in this new clinical study and in an indication where survivin is known to play a critical role in resistance to treatment," said Jeremy Graff Ph.D., Chief Scientific Officer at IMV. "This is a new opportunity not only to explore the clinical benefit of MVP-S in breast cancer patients but also to deepen and enrich our understanding of the MVP-S therapeutic mechanism of action".

Kristina H. Young, M.D., Ph.D., Principal investigator of the study, and Assistant Member, Tumor Microenvironment Lab in the Earle A. Chiles Research Institute, a division of the Providence Cancer Institute commented, "Upregulation of survivin expression in HR+/HER- breast cancer is known to be associated with resistance to aromatase inhibitors. The combination of MVP-S may help overcome this mechanism of resistance and provide benefit to these women while limiting adverse events." She added that "Women with HR+/HER2- breast cancer are in need of treatments that are effective and allow a good quality of life."

About the Study

This investigator-initiated clinical study is a Phase 1b, non-randomized, open-label study to evaluate the combination of maveropepimut-S (MVP-S, formerly named DPX-Survivac) and an aromatase inhibitor with/without radiotherapy or cyclophosphamide (CPA) prior to surgery. Across the three arms of this study, MVP-S will be evaluated in 18 subjects with resectable, non-metastatic HR+/HER2- breast cancer.

The primary objective is to evaluate the safety in this neoadjuvant trial of the combination of maveropepimut-S with an aromatase inhibitor and with/without radiation, or CPA in each arm. The generation of survivin-specific T cells in PBMCs and in tumor tissue both pre and on treatment will be evaluated as secondary objectives. Extensive translational studies will be conducted to explore further the MVP-S mechanism of action in the tumor, the tumor environment and in peripheral circulation. The study is being conducted at the Providence Cancer Institute in Portland, Oregon, and is expected to be completed in 2026 with primary results in 2023. For more information, refer to ClinicalTrials.gov Identifier: NCT04895761.

On November 30, 2021 RedHill Biopharma Ltd. (Nasdaq: RDHL) ("RedHill" or the "Company"), a specialty biopharmaceutical company, reported its financial results and operational highlights for the third quarter ended September 30, 2021 (Press release, RedHill Biopharma, NOV 30, 2021, View Source [SID1234596275]).

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Dror Ben-Asher, RedHill’s Chief Executive Officer, said: "Our U.S. commercial business continues to drive growth, delivering a second consecutive quarterly net revenue record of $21.6 million despite the continuously challenging pandemic environment. Talicia generated another record quarter with 15% growth in new prescriptions, while Movantik continues to perform adding a 1.1% increase to new prescriptions. Both products are also continuing to make strides in gaining both commercial and government formulary coverage. In addition, gross margin increased from 51% in the second quarter to 57% in the third quarter. The Company has successfully attracted a strategic investment from South Korea’s Kukbo and continues to demonstrate responsible financial discipline across the entire business as we strive to achieve our long-term growth aims."

Mr. Ben-Asher added: "Given the recent emergence of the heavily mutated Omicron variant as well as likely emergence of other variants over time, the importance of drug candidates that act independently of the viral spike protein is growing. This makes both opaganib and RHB-107’s host-targeted mechanism of action, and expected maintenance of effect against new variants, increasingly more relevant in the battle against COVID-19. This quarter saw significant focus on our opaganib Phase 2/3 COVID-19 study. The initial top-line results demanded further investigation and our rigorous post-hoc analysis provided much greater clarity into the potential of novel, orally-administered opaganib in the underserved hospitalized moderately severe patient group. This is a group of patients for which no novel therapeutic pill has shown a benefit until opaganib, which demonstrated a 62% reduction in mortality, improved return to room air and earlier hospital discharge for opaganib-treated patients. The results of this analysis, in a group of more than half the total study population, were consistent with what we had seen in our Phase 2 study and compassionate use experience. Despite being a post-hoc analysis, the consistency across multiple endpoints and territories provides us with a high degree of confidence in the results showing opaganib’s effect in this patient population. This analysis also shed light on key issues of the COVID-19 disease severity classification, suggesting that FiO2 might be an improved method for classifying disease severity and predictor of treatment outcome. We have now provided regulators in various countries with all the necessary data to facilitate discussions on the next steps and we continue to provide the data to regulators in additional countries."

"In parallel, we continue to progress our Phase 2/3 study in the U.S. and South Africa with our other novel, once-daily, oral COVID-19 antiviral drug candidate, RHB-107, which has now completed enrollment for Part A of the study, with top-line results expected in the first quarter of 2022. Our Phase 3 study of RHB-204 in pulmonary nontuberculous mycobacteria (NTM) disease continues to enroll patients in the U.S. and progress with Phase 3-stage RHB-104 for Crohn’s disease is expected to speed up thanks to recent, much-awaited, potential progress in Mycobacterium avium subspecies paratuberculosis (MAP) detection research2."

"With a steep reduction in quarterly operating and net loss and continued commercial business growth, leading to a potential commercial operational breakeven before the end of the year, coupled with advanced, exciting and timely R&D pipeline progress, I believe RedHill is well positioned for short, medium and long-term success."

2

Financial highlights for the quarter ended September 30, 20213

Net Revenues were $21.6 million for the third quarter of 2021, as compared with $21.5 million for the second quarter of 2021. The increase is attributable to an increase in sales of Talicia and Movantik, partially offset by an increase in gross-to-net deductions, mainly commercial rebates and Medicare discounts.

Gross Profit was $12.4 million for the third quarter of 2021, compared to $10.9 million for the second quarter of 2021 – an increase of 14%. Gross margin increased from 51% in the second quarter of 2021 to 57% in the third quarter of 2021. The increase in gross profit was mainly attributable to a reversal of inventory write-off recognized in the third quarter of 2021 following the FDA approval of an extension to Talicia stock expiration date.

Research and Development Expenses were $5.8 million for the third quarter of 2021, a decrease of $4.5 million, a 44% reduction compared to the second quarter of 2021, mainly attributable to the completion of our global COVID-19 Phase 2/3 study with opaganib.

Selling, Marketing and General and Administrative Expenses were $24 million for the third quarter of 2021, a decrease of $1.5 million compared to the second quarter of 2021. The decrease was mainly attributable to expenses related to share-based compensation in the previous quarter.

Operating Loss and Net Loss were $17.4 million and $21.4 million, respectively, for the third quarter of 2021 compared to $24.9 million and $29.1 million, respectively, in the second quarter of 2021. The decrease was mainly attributable to the Talicia inventory expiration date extension, completion of our opaganib Phase 2/3 COVID-19 study and a decrease in expenses related to share-based compensation, as detailed above.

Net Cash Used in Operating Activities was $19 million for the third quarter of 2021, similar to the second quarter of 2021.

Net Cash Used in Financing Activities was $1 million for the third quarter of 2021, comprised primarily of payables with respect to the Movantik acquisition, partially offset by proceeds from utilization of ATM and from exercise of options.

Cash Balance as of September 30, 2021, was $51.5 million.

3
Additional Financial Highlights

In November 2021, the Company announced that it had entered into a strategic agreement with Kukbo Co. Ltd., a South Korean corporation, for the sale of RedHill’s American Depositary Shares (ADSs) in a private placement of up to $10 million, of which the first tranche of $5 million has been paid. As part of the agreement, the Company granted Kukbo a six month right of first offer for a license with respect to one or more of opaganib, RHB-107 (upamostat) and Talicia for South Korea and other Asian territories.

In addition, this month, the Company completed an underwritten public offering of approximately 4.7 million ADSs for gross proceeds of approximately $15.5 million, led by Cantor Fitzgerald.

Commercial Highlights

Movantik (naloxegol)4
The Company’s focus on driving Movantik performance and strengthening of market share continues unabated, resulting in another quarter of new prescription growth, increasing by 1.1% compared to the previous quarter.

The Company has achieved significant market access successes with U.S. major payors, continuing to increase the levels of payor coverage.

In July, one of America’s largest payors, serving many Blue Cross and Blue Shield Plans and more than 30 million members, had added Movantik as a preferred brand with no restrictions to its Commercial NetResults "A" series formularies and as a preferred brand on its other commercial formularies starting July 1, 2021. In April, Movantik was also included on the Part D formulary of another major payor with no restrictions. Almost 9 out of 10 U.S. commercial lives are now covered, and we continue to work toward additional formulary coverage for the remaining patients.

In September 2021 RedHill Biopharma Inc., AstraZeneca AB, AstraZeneca Pharmaceuticals LP and Nektar Therapeutics entered into a settlement and license agreement with Aurobindo Pharma USA, Inc. resolving their patent litigation in the U.S. in response to Aurobindo’s Abbreviated New Drug Application (ANDA) seeking approval by the FDA to market a generic version of Movantik. This follows the previously announced resolution of the Apotex litigation and brings to a close all presently pending Movantik patent litigation brought pursuant to The Drug Price Competition and Patent Term Restoration Act (the Hatch-Waxman Act). The earliest licensed entry date of any generic naloxegol in the U.S. is October 1, 2030.

Talicia (omeprazole magnesium, amoxicillin and rifabutin)5
Talicia achieved another record quarter, delivering a 15% increase in new prescriptions, compared to the previous quarter, reflecting 117% growth of Talicia as compared to Q3/2020.

In October, Medi-Cal – California’s Medicaid Health Care program covering two million beneficiaries – had added Talicia to its Contract Drug List (CDL) for H. pylori treatment, with no prior authorization required. This coverage is expected to expand to 14 million beneficiaries on January 1, 2022. During the same month, a new U.S. Patent covering Talicia was granted. This patent reinforces the protection for Talicia through 2034, and the Company has listed this patent in the FDA’s Approved Drug Products with Therapeutic Equivalence Evaluations, or Orange Book.

4
In July, the Company significantly expanded commercial coverage for Talicia, announcing that OptumRx, part of the UnitedHealth Group, a leader in healthcare coverage, partnered with more than 1.3 million healthcare professionals and 6,500 hospitals, had added Talicia to its Commercial Formulary as an unrestricted brand for H. pylori treatment, effective July 1, 2021. This agreement expanded access to Talicia to 26 million additional Americans and increased overall patient access to Talicia to greater than 8 out of 10 covered U.S. Commercial lives.

Aemcolo (rifamycin)6
The Company has maintained promotion of Aemcolo in the third quarter of 2021 supporting the initial momentum that Aemcolo was generating pre-COVID-19 travel restrictions. RedHill and Cosmo Pharmaceuticals N.V are currently in discussions with respect to the amendment of the Aemcolo License Agreement.

R&D Highlights

COVID-19 Program: Opaganib (ABC294640)7
In September 2021, the Company announced top-line results from the global 475-patient Phase 2/3 study in hospitalized patients with severe COVID-19 pneumonia (NCT04467840). Whilst results showed consistent trends in favor of the opaganib arm, the study endpoints did not achieve statistical significance.

A post-hoc analysis of data from 251 study participants requiring a Fraction of inspired Oxygen (FiO2) up to 60% at baseline (54% of the study participants), was subsequently reported in October 2021, demonstrating that treatment with oral opaganib resulted in a 62% reduction in mortality as well as improved outcomes in time to room air and median time to hospital discharge, in this large group of hospitalized, moderately severe COVID-19 patients.

The results provide a strong rationale for opaganib’s potential efficacy in hospitalized patients in need of oxygen supplementation up to 60% FiO2, a large proportion of hospitalized COVID-19 patients. The Phase 2/3 study results are also consistent with opaganib’s earlier U.S Phase 2 study results and the demonstrated potent antiviral inhibition of SARS-CoV-2 variants in human bronchial epithelial cells, providing further support for its potential in earlier stages of disease where viral load is higher.

Additional new preclinical results demonstrating opaganib’s efficacy in significantly decreasing renal fibrosis in a unilateral ureteral obstruction-induced renal interstitial fibrosis mode were also reported by the Company in September 2021.

5
The Company has submitted data packages for opaganib to the regulatory agencies in the U.S., EU, UK and other territories, ahead of planned regulatory advice, with the European Medicines Agency (EMA) having provided expedited evaluation process timelines. As previously stated, additional studies to support the potential of such applications and the use or marketing of opaganib are likely to be required. For example, the FDA has previously indicated that we will need to complete additional studies to support applications in the U.S. The strength of the safety and efficacy data generated from the opaganib studies will be key to regulatory applications.

The Company also continues its discussions with U.S. and other government agencies and non-governmental organizations around potential funding to support the ongoing development of opaganib. Discussions are also ongoing with potential partners who are interested in the rights to opaganib in various territories.

COVID-19 Program: RHB-107 (upamostat)8
RedHill continues to advance the Phase 2/3 study of novel, once-daily, orally-administered, antiviral drug candidate, RHB-107, in the treatment of non-hospitalized patients with symptomatic COVID-19 in the early course of the disease who do not require supplemental oxygen – the vast majority of COVID-19 patients. The study plans to test for the Omicron variant.

Further to announcing in September 2021 that South Africa had joined the U.S. in approving the Phase 2/3 study, along with the expansion to additional U.S. sites, the Company announced this month that the last patient had been enrolled in Part A of the Phase 2/3 study. The study is a 2-part trial designed to evaluate time to sustained recovery from illness as the primary endpoint and for dose selection. A total of 61 patients have been enrolled in Part A and based on safety and tolerability results of part A, a dose for part B will be selected. Top-line results from Part A of the study are expected in the first quarter of 2022, with Part B of the study expected to follow subsequent to discussions with regulators.

RHB-204 – Pulmonary Nontuberculous Mycobacteria (NTM) Disease
A U.S. Phase 3 study is ongoing to evaluate the efficacy and safety of RHB-204 in adults with pulmonary NTM disease caused by Mycobacterium avium Complex (MAC) infection. The Company is also assessing potential expansion of the RHB-204 Phase 3 study to additional territories.

The Company previously announced that the FDA granted Fast Track designation for RHB-204, providing early and frequent communications and a rolling review of any New Drug Application (NDA). RHB-204 is also eligible for NDA Priority Review and Accelerated Approval.

RHB-204 was granted FDA Orphan Drug designation and Qualified Infectious Disease Product designation, extending its U.S. market exclusivity to a potential total of 12 years upon potential FDA approval.

6
RHB-104 – Crohn’s Disease
Based on recent published research, potential progress in Mycobacterium avium subspecies paratuberculosis (MAP) diagnostic technology may enable us to advance the program towards a confirmatory study in approximately 150 MAP positive moderate-severe Crohn’s patients, subject to required regulatory input.

Opaganib – Prostate Cancer and Cholangiocarcinoma
In August 2021, we announced that, based on a preliminary review of partial and unaudited data, the ongoing Phase 2 study for prostate cancer had met its primary endpoint of at least six subjects demonstrating disease control (defined as stable disease or better after 16 weeks on treatment) among at least 27 evaluable subjects. Upon further review and analysis of the unaudited data, the Company reported that the study did not meet its primary endpoint in the study arm evaluating opaganib in combination with enzalutamide. Patient enrolment continues for the study’s other arm, evaluating a combination of opaganib and abiraterone. Accrual and data entry are ongoing and results for the study remain subject to further review and analysis.

The Phase 2a study evaluating the activity of opaganib in advanced cholangiocarcinoma (bile duct cancer) is ongoing at Mayo Clinics in Arizona and Minnesota, Emory University and the Huntsman Cancer Institute at the University of Utah. Enrollment has been completed for the first cohort of 39 patients, evaluating the activity of orally-administered opaganib as a stand-alone treatment. Preliminary data from this cohort indicated a signal of activity in a number of subjects with advanced cholangiocarcinoma. Enrollment is ongoing for a second cohort, evaluating opaganib in combination with hydroxychloroquine, an anti-autophagy agent.

Conference Call and Webcast Information:

The Company will host a webcast today, Tuesday, November 30, 2021, at 8:30 a.m. EST, during which it will present key highlights for the third quarter of 2021.

The webcast including slides will be broadcast live on the Company’s website, View Source, and will be available for replay for 30 days.

To participate in the conference call, please dial one of the following numbers 15 minutes prior to the start of the call: United States: +1-877-870-9135; International: +1-646-741-3167 and Israel: +972-3-530-8845; the access code for the call is: 9753927.

On November 30, 2021 Secura Bio, Inc. (Secura Bio) – (www.securabio.com), an integrated pharmaceutical company dedicated to the worldwide development and commercialization of impactful oncology therapies, reported that, based on discussions with the U.S. Food and Drug Administration (FDA), Secura Bio has submitted to FDA for the withdrawal of the approval of NDA 205353 for FARYDAK (panobinostat) oral capsules (Press release, Secura Bio, NOV 30, 2021, View Source;panobinostat-nda-301434428.html [SID1234596295]). FARYDAK received accelerated approval in February 2015 for use in combination with bortezomib and dexamethasone to treat patients with multiple myeloma who have received at least two prior regimens, including bortezomib and an immunomodulatory agent. Secura Bio acquired FARYDAK in March 2019.

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The accelerated approval was based on progression-free survival and consistent with FDA regulations, required further adequate and well-controlled clinical studies to verify and describe the product’s clinical benefit. In its withdrawal submission, Secura Bio noted that, as previously discussed with FDA, it was not feasible for the company to complete the required post-approval clinical studies as designed as part of the accelerated approval process. Because those studies were required to verify and describe the clinical benefit of the drug product, the clinical benefit of FARYDAK has not been confirmed under the specific constraints of the accelerated approval process.

Because of the withdrawal submission, FARYDAK will no longer be discussed at the December 2, 2021 meeting of the Oncologic Drugs Advisory Committee. As provided for by FDA regulations, Secura Bio anticipates FDA publishing a Federal Register notice announcing withdrawal of the approval.

Secura Bio and its partners will continue to market FARYDAK in other markets where it has been approved.

About FARYDAK (panobinostat)

INDICATION

FARYDAK (panobinostat) capsules, a histone deacetylase inhibitor, in combination with bortezomib and dexamethasone, is indicated for the treatment of patients with multiple myeloma who have received at least 2 prior regimens, including bortezomib and an immunomodulatory agent. This indication is approved under accelerated approval based on progression-free survival. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials

IMPORTANT SAFETY INFORMATION

WARNING: FATAL AND SERIOUS TOXICITIES: SEVERE DIARRHEA AND CARDIAC TOXICITIES

Severe diarrhea occurred in 25% of FARYDAK treated patients. Monitor for symptoms, institute anti-diarrheal treatment, interrupt FARYDAK and then reduce dose or discontinue FARYDAK.

Severe and fatal cardiac ischemic events, severe arrhythmias, and ECG changes have occurred in patients receiving FARYDAK. Arrhythmias may be exacerbated by electrolyte abnormalities. Obtain ECG and electrolytes at baseline and periodically during treatment as clinically indicated.

Diarrhea

Severe diarrhea occurred in 25% of patients treated with FARYDAK (panobinostat) capsules. Diarrhea of any grade occurred in 68% of patients treated with FARYDAK compared with 42% of patients in the control arm. Diarrhea can occur at any time. Ensure patients have antidiarrheal medications on hand, and initiate antidiarrheal medication at the onset of diarrhea
Monitor hydration status and electrolyte blood levels at baseline, and weekly (or more often as clinically indicated) during therapy, and correct to prevent dehydration and electrolyte disturbances
Interrupt FARYDAK at the onset of moderate diarrhea (4-6 stools/day
For life-threatening diarrhea (grade 4), permanently discontinue FARYDAK and bortezomib
For severe diarrhea (≥7 stools/day), or IV fluids or hospitalization required (grade 3), interrupt FARYDAK and bortezomib until resolved and restart both at reduced doses
For moderate diarrhea (4-6 stools/day, grade 2), interrupt FARYDAK until resolved and restart at same dose. Consider interruption of bortezomib until resolved and restart at same dose
Cardiac Toxicities

Arrhythmias occurred in 12% of patients treated with FARYDAK compared with 5% of patients in the control arm. Cardiac ischemic events occurred in 4% of patients treated with FARYDAK compared with 1% of patients in the control arm
Do not initiate FARYDAK treatment in patients with history of recent myocardial infarction or unstable angina
ECG abnormalities such as ST-segment depression and T-wave abnormalities occurred more frequently in patients receiving FARYDAK compared with the control arm: 22% vs 4% and 40% vs 18%, respectively
FARYDAK may prolong QT interval. Do not initiate treatment with FARYDAK in patients with a QTcF >450 msec or clinically significant baseline ST-segment or T-wave abnormalities
Arrhythmias may be exacerbated by electrolyte abnormalities. If during treatment with FARYDAK, the QTcF increases to ≥480 msec, interrupt treatment. Correct any electrolyte abnormalities. If QT prolongation does not resolve, permanently discontinue treatment. Obtain ECG at baseline and periodically during treatment. Monitor electrolytes during treatment with FARYDAK, and correct abnormalities as clinically indicated
Hemorrhage

Fatal and serious cases of gastrointestinal and pulmonary hemorrhage occurred
In the phase 3 registration trial, 5 patients receiving FARYDAK, compared with 1 patient in the control arm, died due to a hemorrhagic event. All 5 patients had grade ≥3 thrombocytopenia at the time of the event
Grade 3/4 hemorrhage was reported in 4% of patients treated with FARYDAK and 2% of patients in the control arm
Monitor platelet counts and transfuse as needed
Myelosuppression

FARYDAK causes myelosuppression including severe thrombocytopenia, neutropenia, and anemia. Obtain a baseline CBC, and monitor the CBC weekly during treatment (or more often if clinically indicated or in patients >65 years of age)
Thrombocytopenia
In the phase 3 registration trial, 67% of patients treated with FARYDAK developed Grade 3/4 thrombocytopenia compared with 31% in the control arm
Thrombocytopenia led to treatment interruption and/or dose modification in 31% of patients receiving FARYDAK
For patients receiving FARYDAK, 33% required platelet transfusion
For patients with platelet count <50 x 109/L with bleeding (grade 3) or <25 x 109/L (grade 4)
Interrupt FARYDAK therapy and monitor platelets at least weekly until ≥50 x 109/L, and restart at reduced dose
Interrupt bortezomib until thrombocytopenia resolves ≥50 x 109/L
If only 1 dose of bortezomib was omitted prior to correction to these levels, restart bortezomib at same dose
If ≥2 doses were omitted consecutively, or within the same cycle, restart at a reduced dose
For patients with platelet count <50 x 109/L (grade 3), maintain FARYDAK and bortezomib doses and monitor platelet counts at least weekly
For patients with severe thrombocytopenia, consider platelet transfusions
Discontinue FARYDAK if thrombocytopenia does not improve despite the recommended treatment modifications or if repeated platelet transfusions are required
Neutropenia
Severe neutropenia occurred in 34% of patients treated with FARYDAK compared with 11% of patients in the control arm
Neutropenia led to treatment interruption and/or dose modification in 10% of patients receiving FARYDAK
Use of granulocyte-colony stimulating factor (G-CSF) was 13% in patients treated with FARYDAK (panobinostat) capsules
For patients with ANC <0.5 x 109/L (grade 4)
Interrupt FARYDAK and bortezomib therapy until ANC is ≥1.0 x 109/L. Restart FARYDAK at reduced dose
If only 1 dose of bortezomib was omitted prior to correction to these levels, restart at same dose. If ≥2 doses of bortezomib were omitted consecutively, or within the same cycle, restart at reduced dose
For patients with ANC <1.0 x 109/L (grade 3) and febrile neutropenia (any grade)
Interrupt FARYDAK and bortezomib therapy until febrile neutropenia is resolved and ANC >1.0 x 109/L
Restart FARYDAK at reduced dose
If only 1 dose of bortezomib was omitted prior to correction to these levels, restart at same dose. If ≥2 doses of bortezomib were omitted consecutively, or within the same cycle, restart at reduced dose
For patients with ≥2 occurrences of ANC between 0.5 – 0.75 x 109/L (grade 3)
Interrupt FARYDAK therapy until ANC ≥1.0 x 109/L, and restart at same dose
Maintain bortezomib dose
For patients with ANC between 0.75 – 1.0 x 109/L (grade 3)
Maintain FARYDAK and bortezomib doses
For grade 3 or 4 neutropenia, consider dose reduction and/or the use of growth factors
Discontinue FARYDAK if neutropenia does not improve despite dose modifications, CSF, or in case of severe infection
Anemia
For patients with hemoglobin <8 g/dL (grade 3), interrupt FARYDAK until hemoglobin ≥10 g/dL. Restart at reduced dose
Infections

Severe infections occurred in 31% of patients (including 10 deaths) treated with FARYDAK compared with 24% of patients (including 6 deaths) in the control arm
FARYDAK treatment should not be initiated in patients with active infections
Monitor patients for signs and symptoms of infections during treatment; if a diagnosis of infection is made, institute appropriate anti-infective treatment promptly and consider interruption or discontinuation of FARYDAK
Hepatotoxicity

Hepatic dysfunction, primarily elevations in aminotransferases and total bilirubin, occurred in patients treated with FARYDAK
Monitor liver function prior to and regularly during treatment. If abnormal liver function tests are observed, consider dose adjustments. Follow patient until values return to normal or pretreatment levels
Avoid use in patients with severe hepatic impairment
Reduce the starting dose of FARYDAK to 15 mg or 10 mg in patients with mild or moderate hepatic impairment, respectively
Embryo-Fetal Toxicity

FARYDAK can cause fetal harm when administered to a pregnant woman
If FARYDAK is used during pregnancy, or if the patient becomes pregnant while taking FARYDAK, the patient should be apprised of the potential hazard to the fetus
Advise females of reproductive potential to avoid becoming pregnant while taking FARYDAK
Advise sexually active females of reproductive potential to use effective contraception while taking FARYDAK, and for at least 3 months after the last dose of FARYDAK
Advise sexually active men to use condoms while on treatment, and for at least 6 months after their last dose of FARYDAK
DRUG INTERACTIONS

Reduce dose to 10 mg when coadministered with strong CYP3A inhibitors. Instruct patients to avoid star fruit, pomegranate or pomegranate juice, and grapefruit or grapefruit juice
Avoid the concomitant use of strong CYP3A inducers
Avoid coadministration with sensitive CYP2D6 substrates or CYP2D6 substrates that have a narrow therapeutic index. If concomitant use of CYP2D6 substrates is unavoidable, monitor patients frequently for adverse reactions
Concomitant use of antiarrhythmic medicines, and other drugs that are known to prolong the QT interval, is not recommended. Antiemetic drugs with known QT-prolonging risk can be used with frequent ECG monitoring
ADVERSE REACTIONS

The most common adverse reactions (incidence of at least 20%) in clinical studies are diarrhea, fatigue, nausea, peripheral edema, decreased appetite, pyrexia, and vomiting
The most common nonhematologic laboratory abnormalities (incidence ≥40%) are hypocalcemia, hypophosphatemia, hypoalbuminemia, hypokalemia, hyponatremia, and increased creatinine. The most common hematologic laboratory abnormalities (incidence ≥60%) are thrombocytopenia, lymphopenia, leukopenia, neutropenia, and anemia
Serious adverse events (SAEs) occurred in 60% of patients in the FARYDAK arm. The most frequent (≥5%) treatment-emergent SAEs reported for patients treated with FARYDAK were pneumonia, diarrhea, thrombocytopenia, fatigue, and sepsis

On November 30, 2021 Chimeric Therapeutics (ASX:CHM, "Chimeric" or the "Company"), a clinical-stage cell therapy company and the ASX leader in cell therapy, reported that it has entered into an exclusive option to license agreement with Case Western Reserve University (CWRU) for a Clinically validated, Off the shelf, Robust, Enhanced Natural Killer (CORE-NK) cell platform – a platform technology that provides the optimal foundation for the development of multiple next generation NK and CAR-NK products (Press release, Chimeric Therapeutics, NOV 30, 2021, View Source [SID1234596312]).

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Natural killer (NK) cells have innate safety features and the natural ability to target and destroy cancer cells through both indirect and direct mechanisms. The challenge with natural killer (NK) cells is that they are not naturally abundant or active enough to overcome cancer.

Dr. David Wald, a leading expert in immuno-oncology at Case Western Reserve University in Ohio, USA designed and developed the CORE-NK platform, enhancing the natural anti-cancer properties of NK cells to be robust and active enough to overcome cancer.

The CORE-NK platform utilizes a foundation of healthy donor NK cells, activating and expanding them to establish an enhanced, off the shelf NK cell platform that can provide an abundant supply of highly active NK cells. Preclinical data on the CORE-NK platform was published in the prestigious family of Nature publications in 2019.

In May 2018 a phase 1 clinical trial was initiated at the Case Comprehensive Cancer Center to study the CORE-NK platform in patients with both solid tumours and blood cancers. The phase 1 clinical trial of the CORE-NK platform was completed in June 2021 with clinical data expected in 2022. The trial examined the safety, bioactivity and efficacy of the CORE-NK platform cells at 3 dose levels in patients with both blood cancers and solid tumours.

With the clinical validation from the phase 1 trial complete, the CORE-NK platform provides the ideal off the shelf platform for the development of next generation NK and CAR-NK products.

Chimeric intends to begin a research collaboration with CWRU to further enhance and engineer the CORE-NK platform cells to develop a next generation CORE-NK platform and three initial CAR-NK products.

"The clinical experience we’ve had with the CORE-NK platform gives us tremendous confidence in the development path for optimized NK and CAR NK products. We look forward to working in close collaboration with Chimeric to bring forward the next generation of NK and CAR NK products to the clinic," said Dr. Wald, MD, PhD, Associate Professor of Pathology Case Western Reserve University School of Medicine and Member, Immune Oncology Program, Case Comprehensive Cancer Center, Associate Director for Basic Research, University Hospitals, Wesley Center for Immunotherapy.

The next generation CORE-NK platform will be developed with enhanced activation and expansion features with plans to study it as a combination therapy in blood cancers.

Three initial CAR-NK products will be developed using the next generation CORE-NK platform as a backbone leveraging Chimeric’s existing pipeline of chimeric antigen receptors (CARs); a CLTX CAR-NK (CHM 1301), a CDH17 CAR-NK (CHM 2301) and a currently undisclosed target CAR-NK (CHM 3301).

Chimeric will also explore additional opportunities to further leverage the CORE-NK platform to develop additional NK and CAR NK products through internal development and/or partnerships with other biotech and pharmaceutical companies.

This strategic agreement is transformative for Chimeric propelling the company forward as the Australian leader in cell therapy and as an emerging global cell therapy company with a robust and advanced portfolio of innovative autologous (personalized) and allogeneic (off the shelf) NK and T cell assets.

"The CORE-NK platform is truly transformative for Chimeric. It provides us with a platform technology that triples our current portfolio by enabling us to accelerate the development of multiple new, off the shelf, NK cell assets that work in perfect synergy with our existing pipeline. We could not be more excited to be bringing the CORE-NK platform into our portfolio and to be working in collaboration with Dr. Wald and the expert team at CWRU. Their clinical trial experience with the CORE-NK platform and their expertise in the development of NK cells will catapult our development forward," said Jennifer Chow, CEO Chimeric Therapeutics.

Under the terms of the option agreement, Chimeric has the exclusive right to license the CORE-NK platform for development and commercialization in cancer. Chimeric intends to rapidly move to complete full licensing of the platform and expects to pay CWRU development milestones and industry standard royalty payments based on commercial net sales. Upfront fees associated with the option agreement will be funded entirely from existing cash reserves.

The area of natural killer cells has seen widespread investment and partnership interest with numerous large transactions involving companies such as Merck, Takeda, Janssen and Kite.

Investor webinar

Chimeric Therapeutics CEO and Managing Director Jennifer Chow will hold an investor webinar today, Wednesday 1 December 2021, at 11am AEDT to elaborate on this announcement and take questions.

Click the link below to register:
View Source

After registering, you will receive a confirmation email about how to join the webinar. A recording of the webinar will be available at the same link shortly after the conclusion of the session.