On November 15, 2021 Redx Pharma (AIM: REDX), the clinical-stage biotechnology company focused on discovering and developing novel, small molecule, highly targeted therapeutics for the treatment of cancer and fibrotic disease, reported that the first patient has been dosed in the monotherapy arm of the Phase 2 clinical trial of its investigational drug RXC004 in patients with advanced microsatellite stable (MSS) metastatic colorectal cancer (mCRC) who have progressed following treatment with standard of care (Press release, Redx Pharma, NOV 15, 2021, View Source [SID1234595549]). RXC004 is Redx’s wholly-owned, highly potent and selective, orally active once-daily Porcupine inhibitor being developed as a targeted therapy for Wnt-ligand driven cancer.

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The multi-centre Phase 2 clinical trial (clinicaltrials.gov NCT04907539) will evaluate preliminary efficacy and safety of RXC004 in genetically-selected patients with Ring finger protein 43 (RNF43) or R-spondin (RSPO) aberrated, advanced MSS mCRC. Topline data is expected to report in the first half of 2023.

A second arm of the trial, evaluating RXC004 in combination with the anti-PD-1 antibody nivolumab in patients with MSS mCRC, is expected to commence in the first half of 2022 once a recommended dose has been established in the ongoing Phase 1 dose escalation combination trial.

D r Natalie Cook, University of Manchester and Christie NHS Foundation Trust, UK, and International Coordinating Investigator of the study in the UK, commented: "Microsatellite stable metastatic colorectal cancer is a devastating disease, with limited treatment options. A subgroup of these colorectal cancers possess RNF43 mutations or RSPO fusions leading to activation of the Wnt pathway as a driver of the cancer. This study will assess whether RXC004, a novel Porcupine inhibitor, has a clinically meaningful anti-cancer effect in this well-defined patient cohort.”

Lisa Anson, Chief Executive Officer of Redx Pharma, added: "We are excited to be dosing patients in Redx’s first ever Phase 2 clinical trial of a wholly-owned drug candidate, an important corporate milestone. Our encouraging Phase 1 results, recently reported at the ESMO (Free ESMO Whitepaper) Congress, combined with our preclinical data, strongly support the hypothesis that patients with Wnt-ligand driven tumours could benefit from RXC004."

A second Phase 2 clinical trial evaluating RXC004 as a monotherapy in advanced genetically selected pancreatic cancer and unselected biliary cancer is also expected to start in 2021.

About microsatellite stable metastatic colorectal cancer (MSS mCRC)
Metastatic colorectal cancers have a poor prognosis with a 5-year survival rate of approximately 15% (1). Standard first line and second line treatments are combinations of chemotherapy and a VEGF inhibitor or EGFR inhibitor. MSS cancers account for 95% of metastatic CRC and tend to be unresponsive to treatment with immune checkpoint inhibitors. In the third line treatment setting the response rate to standard agents is <5%, median progression free survival is approximately 2 months and overall survival approximately 6 months (2,3). Approximately 8% of MSS mCRC patients have Wnt-ligand driven tumours (3% RNF43 mutations and 5% RSPO fusions) (4)

About RXC004
RXC004 is a wholly owned, potent, selective, oral, small-molecule inhibitor of the Porcupine enzyme, a key activator of Wnt ligands in the Wnt-signalling pathway. The Wnt pathway is well established as a driver of both tumour growth and immune evasion. Aberrant Wnt signalling contributes directly to tumour growth and plays an important role in immune evasion, which has also been linked to resistance to immune-checkpoint inhibitors (ICIs) such as nivolumab. By selecting patients with tumours that have high Wnt-ligand dependency, such as those with loss of function mutations in the RNF43 gene and fusions in the RSPO gene family, RXC004 has an opportunity to both directly inhibit the tumour growth and have an immune-enhancing effect to allow the patient’s immune system to better recognise and attack the tumour.

ICIs such as anti-PD-1 antibodies have revolutionised the treatment of cancer, but do not work in all patients. Wnt-pathway activation can enhance the ability of the tumour to evade destruction by the immune system and has been linked to lack of response to ICIs in these tumours. Redx scientists have observed in preclinical studies that RXC004 can block activation of the Wnt pathway and restore the ability of the immune system to fight the tumour. Thus, RXC004 offers potential to address some of the shortcomings of ICI therapies through increasing both response rates and duration of response, particularly in patient populations unresponsive to ICI therapy.

On November 15, 2021 Protalix BioTherapeutics, Inc. (NYSE American: PLX) (TASE: PLX), a biopharmaceutical company focused on the development, production and commercialization of recombinant therapeutic proteins produced by its proprietary ProCellEx plant cell-based protein expression system, reported financial results for the third quarter ended September 30, 2021 and provided a financial and business update on recent corporate, clinical and regulatory developments (Press release, Protalix, NOV 15, 2021, View Source [SID1234595548]).

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"We are pleased with the progress we have made over the past few weeks with respect to the regulatory path forward with PRX-102 for the treatment of Fabry disease with both the U.S. Food and Drug Administration and the European Medicines Agency," stated Dror Bashan, Protalix’s President and Chief Executive Officer. "Following our Type A meeting with the FDA, we believe there is now an established pathway to resubmit the PRX-102 BLA. We remain focused on our mission to bring to the market another important potential alternative treatment for all adult Fabry patients. We are grateful for the continued support from our team members, advocates and external partners who remain as steadfast and focused as ever; they see the value of having an alternative treatment for patients, especially one with our profile. Following the note exchange agreement we completed in August, we now have additional financial flexibility and sufficient capital to fund our operations through important milestones in 2022. We are committed to executing our strategy and are looking forward to converting the momentum of the last quarter into a successful 2022."

2021 Third Quarter and Recent Business Update

Regulatory Updates

On October 11, 2021, the Company, together with its development and commercialization partner, Chiesi Farmaceutici S.p.A., or Chiesi, provided a regulatory update regarding PRX-102, which included the announcement of the receipt of the official Type A (End-of-Review) meeting minutes from the U.S. Food and Drug Administration (FDA) regarding the Complete Response Letter (CRL) received in April 2021 for the biologics license application (BLA) for PRX–102 for the treatment of adult patients with Fabry disease, and confirming the pathway for resubmission of a BLA for PRX–102. The PRX–102 biologics license application (BLA) resubmission to the FDA is anticipated in the second half of 2022.
On October 8, 2021, the Company, together with Chiesi, held a meeting with the Rapporteur and Co-Rapporteur of the European Medicines Agency (EMA) regarding PRX-102. At the meeting, Chiesi and the Company discussed the scope of the anticipated Marketing Authorization Application (MAA) submission for the European Union, and the Rapporteur and Co-Rapporteur were generally supportive of a planned MAA submission for PRX-102. This is an important step in the necessary pre-submission activities leading up to a MAA submission. The Company and Chiesi expect to submit an MAA to the EMA for PRX-102 during the first quarter of 2022.
Clinical Advancements

On October 15, 2021, the Company, together with Chiesi, announced the final dosing of the last patient in the Company’s phase III BALANCE clinical trial, or the BALANCE study, for the proposed treatment of Fabry disease. The BALANCE study is a 24-month, randomized, double blind, active control study of PRX-102 in Fabry patients with impaired renal function. Unblinded final data is anticipated to be released in the second quarter of 2022 after all remaining patients have completed the 24-month treatment period.
Given the changed regulatory landscape in the United States, the planned data package for the PRX-102 BLA resubmission will include the final two-year analyses of the BALANCE study.
Corporate & Financial Developments

On August 25, 2021, the Company completed exchanges, or the Exchanges, of a substantial majority of the Company’s outstanding 7.50% Senior Secured Convertible Notes due 2021, or the 2021 Notes, with institutional note holders. In the Exchanges, an aggregate of $54.65 million principal amount of outstanding 2021 Notes were exchanged for an aggregate of $28.75 million principal amount of newly issued 7.50% Senior Secured Convertible Notes due 2024, $25.90 million in cash, and approximately $1.1 million in cash representing accrued and unpaid interest through the closing date of the Exchanges.
The maturity date of the 2021 Notes is November 15, 2021, on which date the Company is required to settle all of the remaining 2021 Notes then outstanding, and pay all accrued but unpaid interest thereon. On November 9, 2021, the Company delivered the necessary funds under the indenture governing the 2021 Notes to effectively discharge the remaining outstanding 2021 Notes.
Third Quarter 2021 Financial Highlights

The Company recorded revenues from selling goods of $4.5 million during the three months ended September 30, 2021, an increase of $1.2 million, or 36%, compared to revenues of $3.3 million for the same period of 2020.
Revenues from license and R&D services for the three months ended September 30, 2021 and September 30, 2020 were $7.5 million. Revenues from license and R&D services are comprised primarily of revenues the Company recognized in connection with its license and supply agreements with Chiesi. A revenue increase of $1.0 million recognized from the Kirin feasibility study was offset by a $1.0 million decrease in revenue generated under the Company’s license and supply agreements with Chiesi.
Cost of goods sold for the three months ended September 30, 2021 was $3.7 million, an increase of $0.8 million, or 28%, compared to $2.9 million for the same period in 2020. The increase resulted primarily from higher sales.
Research and development expenses for the three months ended September 30, 2021 were $7.3 million, a decrease of $0.4 million, or 5%, compared to $7.7 million for the same period of 2020. The decrease was primarily the result of the completion of two out of the three phase III clinical trials of PRX–102 and reduced costs related to the BALANCE study. The Company expects research and development expenses to continue to be its primary expense as it enters into a more advanced stage of preclinical and clinical trials for certain product candidates.
Selling, general and administrative expenses were $3.0 million, an increase of $0.2 million, or 7%, for the three months ended September 30, 2021 compared to $2.8 million for the same period in 2020. The increase is primarily the result of an increase of $0.4 million in corporate costs mainly related to insurance and a $0.2 million increase in sales and marketing costs, partially offset by a decrease of $0.5 million in share-based compensation.
Financial expenses, net, were $2.3 million for the three months ended September 30, 2021 and $1.9 million for the three months ended September 30, 2020. The increase resulted primarily from loss on extinguishment related to the Exchanges of the Company’s 2021 Notes.
Cash, cash equivalents and short-term bank deposits were approximately $48.7 million at September 30, 2021.
Net loss for the three months ended September 30, 2021 was approximately $4.2 million, or $0.09 per share, basic and diluted, compared to a net loss of $4.4 million, or $0.14 per share, basic and diluted, for the same period in 2020.
Conference Call and Webcast Information

The Company will host a conference call today, November 15, 2021, at 8:30 am Eastern Standard Time, to review the corporate, clinical and regulatory developments, which will also be available by webcast. To participate in the conference call, please dial the following numbers prior to the start of the call:

Webcast Details:

Please access the websites at least 15 minutes ahead of the conference to register, download and install any necessary audio software.

The conference call will be available for replay for two weeks on the Events Calendar of the Investors section of the Company’s website, at the above link.

On November 15, 2021 Glycotope GmbH, a biotechnology company developing antibodies against proteins carrying tumor-specific carbohydrate structures, reported it is presenting new data at the 2021 Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) 36th Annual Meeting (Press release, Glycotope, NOV 15, 2021, View Source [SID1234595547]).

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Henner Kollenberg, Managing Director of Glycotope GmbH commented: "The data presented at SITC (Free SITC Whitepaper) underlines our long-standing expertise in the generation, evaluation and pre-clinical development of highly novel antibodies targeting cancer indications. GT-00A x IL15, a TA-MUC1-targeting IL-15 fusion antibody is one of the first tumor-targeted immuno-cytokines. The preclinical data showed that our IL-15 immuno-cytokine has the potential to significantly outperform non-targeted IL-15 immuno-cytokines offering a highly needed alternative in the treatment of several solid-tumor indications. The data for GT-001, a Lewis Y targeting antibody, demonstrated superior specificity compared to previously developed anti-Lewis Y antibodies with the potential of improved efficacy and reduced side effects."

Poster details are as follows:

Abstract Number: 712

Title: Preclinical characterization of GT-00A x IL15: A novel IL-15-based immunocytokine with unique tumor targeting properties
Category: Poster Session: Immune-stimulants and immune modulators

Download: View Source GT-00AxIL15 Poster SIT2021

Abstract Number: 781
Title: GT-001 – anti-Lewis Y antibody with superior fine-specificity and reduced off-target binding

Category: Poster Session: Immuno-conjugates and chimeric molecules

Download: View Source GT-001 Poster SITC (Free SITC Whitepaper)2021

About GT-00A x IL15

GT-00A x IL15 is a TA-MUC1 targeting IL-15 immuno-cytokine fusion antibody. Cytokines have long been used for cancer therapy to activate the immune system, but side effects and short half-life limit their therapeutic application. The concept of specific targeting to the tumor and tumor microenvironment to exploit the full potential of IL-15 biology is unique within the competitive field of IL-15 (super)agonists. The immuno-cytokine attracts and activates immune cells (e.g. T and NK cells) directly at the tumor site thereby turning an "immune desert" into a "hot" tumor and inducing tumor cell lysis. A comprehensive non-clinical data package is available.

About GT-001

GT-001 is a humanized IgG1 mAb with unrivaled fine-specificity, specifically targeting the tumor-associated Lewis Y (LeY, CD174) carbohydrate antigen without cross-reactivity to related carbohydrates expressed on blood cells. GT-001 shows binding to a high percentage of breast cancers, non-small cell lung cancer, colorectal cancer, head and neck cancer, small cell lung cancer and ovarian cancer patient samples. The effective binding and internalization allows for ADC or CAR development.

On November 15, 2021 Celularity Inc. (Nasdaq: CELU) ("Celularity") reported that preclinical data on the development of its novel allogeneic genetically modified human placental CD34+ derived NK cell therapeutic program CYNK-101 (Press release, Celularity, NOV 15, 2021, View Source [SID1234595545]). Celularity reported its findings in a poster presentation at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) Annual Meeting held in Washington, D.C., November 10-14, 2021.

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Poster 159: "Developing placental CD34+-derived natural killer cells with high affinity cleavage resistant CD16 (CYNK-101) and Cetuximab for enhanced therapy of EGFR+ non-small cell lung and head and neck cancers"

Highlights: CYNK-101 is a cryopreserved off the shelf allogeneic NK cell product, overexpressing a high IgG binding affinity, proteinase cleavage resistant, CD16 variant. The results demonstrate the synergistic effect of combining CYNK-101 with Cetuximab to drive antibody dependent cellular cytotoxicity activity against EGFR+ tumors. Further development of the combinational therapy against EGFR+ non-small cell lung cancer and head and neck squamous cell carcinomas is warranted.

On November 15, 2021 Ayala Pharmaceuticals, Inc. (Nasdaq: AYLA), a clinical-stage oncology company focused on developing and commercializing small molecule therapeutics for patients suffering from rare and aggressive cancers, primarily in genetically defined patient populations, reported financial results for the period ended September 30, 2021 and highlighted recent progress and upcoming milestones for its pipeline programs (Press release, Ayala Pharmaceuticals, NOV 15, 2021, View Source [SID1234595544]).

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"As we gear up for multiple important milestones in 2022 across all of our clinical-stage programs in various indications, including desmoid tumors, triple negative breast cancer, adenoid cystic carcinoma and potentially multiple myeloma, we remain steadfast in our approach to developing gamma secretase inhibitors to treat these genetically defined cancers," said Roni Mamluk, Ph.D., Chief Executive Officer of Ayala. "We are incredibly pleased with the safety and efficacy profile of AL101 for the treatment of recurrent/metastatic adenoid cystic carcinoma harboring Notch-activating mutations, as presented at ESMO (Free ESMO Whitepaper) in September, as well as the strong preclinical rationale for potential combination treatment in this indication and other tumor types. We also continued to progress our pivotal RINGSIDE trial evaluating AL102 for the treatment of desmoid tumors as enrollment continues across multiple sites globally and look forward to reporting preliminary results from this trial in mid-2022. In addition, we are very pleased with our ongoing collaboration with Novartis and the status of the study of our AL102 in combination with their anti BCMA agent for multiple myeloma."

Recent Business Highlights and Upcoming Milestones:

Published Two Case Studies Highlighting Clinical Activity of AL101 in Desmoid Tumors in Current Oncology: In September 2021, Ayala published two case studies of adult patients with desmoid tumors treated with AL101. Both patients experienced significant tumor burden and symptomatic and life-threatening disease due to disease bulk and location. With AL101 treatment, both subjects achieved long-lasting partial responses with a maximal decrease in tumor size from baseline of 41% after approximately 1 year (55 weeks) of treatment in Case One, and a maximal decrease in tumor size from baseline of 60% after about 1.6 years (82 weeks) of treatment in Case Two.

On Track to Report Initial Interim Data from Part A of the Pivotal Phase 2/3 RINGSIDE Trial for the Treatment of Desmoid Tumors in Mid-2022: Enrollment continues to progress globally in the Phase 2/3 RINGSIDE Trial of AL102. Ayala expects to report an initial interim data read-out from part A of the trial in mid-2022, with part B of the study commencing thereafter.

Phase 1 Trial of AL102 in Combination with Novartis’ BCMA Targeting Agent, WVT087 for the Treatment of Relapsed/Refractory Multiple Myeloma Continues to Progress: Enrollment progresses as planned in the Phase 1 combination trial of AL102 with Novartis’ investigational anti-B-cell maturation antigen (BCMA) agent, WVT078, for the treatment of relapsed and/or refractory (R/R) multiple myeloma (MM).

Presented Preliminary Clinical Data from the Ongoing Phase 2 ACCURACY Trial and ACC at European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Virtual Congress 2021: In September 2021, Ayala presented updated interim data from the 6mg cohort of its ongoing Phase 2 ACCURACY study of AL101 for the treatment of recurrent/metastatic adenoid cystic carcinoma (R/M ACC) harboring Notch activating mutations. The data demonstrated meaningful clinical activity of AL101 6mg monotherapy with a 70% disease control rate across 33 evaluable patients. Partial responses were observed in three subjects (9%) and stable disease was observed in 20 subjects (61%). The 6mg dose of AL101 was well tolerated with manageable side effects consistent with those observed in the 4mg cohort.

Presented Preclinical Proof of Concept Data of AL101 in Combination with Approved Cancer Therapies in ACC at ESMO (Free ESMO Whitepaper): In September 2021, Ayala also presented a preclinical study evaluating the potential of combination therapy of AL101 in PDX models of ACC, comparing the differential gene expression of ACC tumors versus normal matched tissue regardless of Notch activation status. AL101 in combination demonstrated significant tumor growth inhibition, including regressions, compared to each drug alone, and the study indicated that crosstalk between signaling pathways may increase the efficacy of AL101 in R/M ACC regardless of Notch mutational status.

Phase 2 TENACITY Trial of AL101 for the Treatment of Triple Negative Breast Cancer Continues to Progress: Ayala continues to enroll patients in the Phase 2 TENACITY clinical trial of AL101, for the treatment of patients with Notch-activated recurrent or metastatic (R/M) triple negative breast cancer (TNBC). The Company expects to report preliminary data from this ongoing trial in 2022.

Third Quarter 2021 Financial Results

Cash Position: Cash and cash equivalents were $40.8 million as of September 30, 2021, as compared to $42.0 million as of December 31, 2020.
Collaboration Revenue: Collaboration revenue was $0.6 million for the third quarter of 2021, as compared to $0.7 million for the same period in 2020.
R&D Expenses: Research and development expenses were $7.4 million for the third quarter of 2021, compared to $5.4 million for the same period in 2020. The increase was primarily driven by the advancement in our clinical trials.
G&A Expenses: General and administrative expenses were $2.2 million for the third quarter of 2021, compared to $1.9 million for the same period in 2020.
Net Loss: Net loss was $9.8 million for the third quarter of 2021, resulting in a basic and diluted net loss per share of $0.68. Net loss was $7.4 million for the same period in 2020, resulting in a basic and diluted net loss per share of $0.59.