On November 12, 2021 Aileron Therapeutics (NASDAQ:ALRN), a chemoprotection oncology company focused on fundamentally transforming the experience of chemotherapy for cancer patients, reported financial results and business highlights for the third quarter ended September 30, 2021 (Press release, Aileron Therapeutics, NOV 12, 2021, View Source [SID1234595374]).

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!

"In the third quarter, we continued our clinical progress, reporting final positive results from our chemoprotection proof-of-concept SCLC study and confirming ALRN-6924’s p21-mediated cell cycle arrest in our healthy volunteer study. We also reported healthy volunteer data on time to onset, magnitude and duration of ALRN-6924’s cell cycle arrest, which provides support for a universal dose and schedule across distinct chemotherapy regimens," said Manuel Aivado, M.D., Ph.D., President and Chief Executive Officer at Aileron. "In the year ahead, we anticipate key data readouts from our NSCLC trial, as we continue to advance toward our vision to deliver selective chemoprotection to patients with p53-mutant cancers regardless of type of chemotherapy or cancer."

Dr. Aivado continued, "We recently presented preclinical data demonstrating cell cycle arrest in healthy tissue outside of the bone marrow – namely, epithelial mucosa cells in the GI tract. This is another important strategic building block, as a key characteristic of ALRN-6924’s differentiated profile is the potential to selectively protect multiple tissues and organs from chemotherapy-induced toxicities with a single medicine – representing a potential paradigm shift in the care of millions of cancer patients."

Despite the rise of immunotherapies and targeted therapies, chemotherapy continues to play a central role, at some point in the treatment continuum, for nearly all cancer patients, bringing with it significant toxicities. Aileron is developing ALRN-6924 to selectively protect healthy cells in patients with p53-mutated cancers to reduce or eliminate chemotherapy-induced side effects. Nearly 1 million patients each year are diagnosed with a p53-mutated cancer in the US alone. Aileron employs a precision medicine approach, exclusively treating patients with p53-mutated cancers; ALRN-6924 is designed to selectively protect these patients’ healthy cells from chemotherapy without protecting cancer cells. This novel concept is known as selective chemoprotection. The reduction or elimination of multiple chemotherapy-induced side effects may enhance tolerability of chemotherapy, may result in fewer dose reductions or delays of chemotherapy, and the potential for improved efficacy of chemotherapy. Aileron’s vision is to bring chemoprotection to patients with p53-mutated cancers, which represent approximately 50% of cancer patients, regardless of type of cancer or chemotherapy.

Third Quarter 2021 Highlights and Recent Updates

Continued to progress randomized, double-blind, placebo-controlled Phase 1b clinical trial of ALRN-6924 for the prevention of chemotherapy-induced side effects in patients with advanced p53-mutated NSCLC. Aileron plans to enroll a total of 60 patients with advanced p53-mutated NSCLC undergoing treatment with first-line carboplatin plus pemetrexed with or without immune checkpoint inhibitors. Patients will be randomized 1:1 to receive carboplatin/pemetrexed plus 0.3 mg/kg ALRN-6924 or placebo for at least four 21-day treatment cycles.

Currently, 12 trial sites are open for enrollment in the United States and Europe, and Aileron anticipates opening additional sites. Due to the impact of the COVID-19 Delta variant in Eastern Europe, several sites in this region began screening two months later than planned. With those sites now activated, there has been an associated increase in patient enrollment. As a result of the delay in site activation and patient enrollment, Aileron has updated its guidance for planned data readouts as follows: interim results on 20 patients with four cycles in 2Q22, and topline results on 60 patients with four cycles in 4Q22. The company also plans to conduct a blinded safety evaluation on 10 patients after one cycle in 1Q22 to determine whether the safety and tolerability profile of ALRN-6924 in NSCLC patients is consistent with the safety and tolerability profile observed in previous clinical trials.

For more information, please visit the NSCLC trial listing on clinicaltrials.gov.
Presented new preclinical data at AACR (Free AACR Whitepaper)-NCI-EORTC AACR-NCI-EORTC (Free AACR-NCI-EORTC Whitepaper) International Conference on Molecular Targets and Cancer Therapeutics (EORTC-NCI-AACR) (Free ASGCT Whitepaper) (Free EORTC-NCI-AACR Whitepaper) 2021 supporting potential of chemoprotection in healthy cells beyond bone marrow cells. Aileron presented new preclinical data that demonstrated ALRN-6924’s activity as a radioprotective agent in preclinical mouse models of acute radiation-induced toxicity, leveraging the same mechanism of action – p53 activation and subsequent p21 upregulation as well as p21-induced cell cycle arrest – that has clinically shown protection against chemotherapy-induced bone marrow toxicities.

As part of this poster presentation, Aileron presented preclinical data demonstrating ALRN-6924’s activation of p21-induced cell cycle arrest in murine bone marrow cells as well as in epithelial mucosa cells in the GI tract. ALRN-6924 is the first chemoprotective agent, either in clinical development or marketed, to demonstrate the potential of cell cycle arrest-mediated chemoprotection of bone marrow cells as well as cells outside of bone marrow. These findings are consistent with Aileron’s belief that ALRN-6924 may also selectively protect additional organs and tissues from chemotherapy-induced toxicities.
Presented final data from Phase 1b trial of ALRN-6924 in SCLC patients at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress 2021. Aileron presented final results from its completed Phase 1b trial in patients with p53-mutated SCLC receiving second-line topotecan. Following the interim proof-of-concept data presented in October 2020 from this study, these final results reinforced ALRN-6924’s ‘triple-play’ reduction in neutropenia, thrombocytopenia and anemia caused by chemotherapy, as well as a reduction of platelet and red blood cell transfusions, reported in October 2020.

Presented preliminary data from ALRN-6924 Healthy Volunteer Study at International Society for Experimental Hematology (ISEH) 2021 Scientific Meeting and ESMO (Free ESMO Whitepaper) 2021. Aileron presented preliminary results from its ongoing Phase 1 pharmacology study of ALRN-6924 in healthy volunteers, which confirmed 0.3 mg/kg as the optimal dose for ALRN-6924 and confirmed the drug’s novel p53 biomarker-driven mechanism of action, as well as its pharmacodynamic effects, including time to onset, magnitude and duration.

The healthy volunteer study is evaluating ALRN-6924’s induction of p21-induced cell cycle arrest in healthy, normal bone marrow cells and other cell types in healthy volunteers receiving ALRN-6924. The aim of the study is to develop a universal dosing regimen for ALRN-6924 for use as a chemoprotection agent across a range of chemotherapies and p53-mutated tumor indications. The study is ongoing, and Aileron anticipates presenting additional findings at a later date.
Third Quarter 2021 Financial Results

Cash Position: Cash, cash equivalents and investments on September 30, 2021 were $52.2 million. The company expects, based on its current operating plan, that its existing cash, cash equivalents and investments will fund operations into the second half of 2023.

Research and Development (R&D) Expenses: R&D expenses for the quarter ended September 30, 2021 were $4.3 million, compared to $2.7 million for the quarter ended September 30, 2020. The increase of $1.6 million primarily resulted from increased spending of $0.5 million related to clinical development of ALRN-6924 for the company’s Phase 1b clinical trial in patients with advanced NSCLC and the company’s Phase 1 trial of ALRN-6924 in healthy human volunteers, $0.7 million of ALRN-6924 manufacturing costs, $0.3 million of higher employee-related costs, and $0.2 million in non-clinical research costs, all partially offset by lower facility costs.

General and Administrative (G&A) Expenses: G&A expenses for the quarter ended September 30, 2021 were $2.5 million compared to $2.3 million for the quarter ended September 30, 2020. Increased G&A expenses were primarily the result of higher employee-related costs partially offset by lower facility costs.

Net Loss: Net loss for the quarter ended September 30, 2021 was $6.7 million, compared to $5.0 million for the corresponding quarter in 2020. The basic and diluted net loss per share for the third quarter of 2021 was $0.07 compared to $0.13 for the third quarter of 2020. The change in basic and diluted net loss per share is primarily a result of increased shares outstanding as a result of sales of common stock during the first quarter of 2021 partially offset by higher operating expense.

On November 12, 2021 Elevation Oncology, Inc. (Nasdaq: ELEV), a clinical stage biopharmaceutical company focused on the development of precision medicines for patients with genomically defined cancers, reported financial results for the quarter ended September 30, 2021 (Press release, Elevation Oncology, NOV 12, 2021, View Source;utm_medium=rss&utm_campaign=elevation-oncology-reports-third-quarter-2021-financial-results [SID1234595390]).

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 third quarter was marked by continued progress on our mission to bring purpose-built medicines to patients with genomically defined cancers," said Shawn M. Leland, PharmD, RPh, Founder and Chief Executive Officer of Elevation Oncology. "The CRESTONE Study is now open and enrolling patients in the US, Canada, and Australia. Our collaboration with Caris Life Sciences is revealing a series of potential programs targeting genomic fusions. Finally, I am also pleased to welcome Valerie Malyvanh Jansen, MD, PhD, as our first Chief Medical Officer."

"We are encouraged by the durable clinical benefit seen with seribantumab in the case study of a patient with metastatic pancreatic cancer harboring an NRG1 fusion that was presented at the Australasian Gastro-Intestinal Cancer Trials Group conference," said Dr. Jansen. "Separately, we expect to complete enrollment of the first 20 patients in Cohort 1 of CRESTONE in mid-2022. We also anticipate presenting initial clinical data at a major medical meeting in mid-2022, which will include results from approximately 10 patients from Cohort 1 with meaningful follow-up who have been treated with seribantumab at 3 grams weekly."

Recent Business Highlights

Seribantumab

Case study of a patient with pancreatic cancer treated with seribantumab under a compassionate use program highlighted a confirmed partial response and durable clinical benefit, representing the first clinical data presented on the use of seribantumab in a patient with a tumor harboring an NRG1 fusion. Treatment with seribantumab was included as part of a case series presentation at the Australasian Gastro-Intestinal Trials Group (AGITG) 2021 Annual Scientific Meeting in October. A patient with treatment-refractory metastatic pancreatic cancer who had their tumor genomically profiled through the Cancer Molecular Screening and Therapeutics (MoST) program, was found to harbor an NRG1 fusion, and subsequently received treatment with seribantumab through a compassionate use program provided by Elevation Oncology. As of the data cut-off for the presentation, treatment with seribantumab resulted in durable clinical benefit for over 9 months, an approximately 90% reduction in the cancer biomarker CA19-9, and an ongoing 3 month confirmed partial response per RECIST criteria with a maximum tumor reduction of over 50%.
Launched additional global clinical trial sites in CRESTONE. The Company recently launched new clinical trial sites in Canada and Australia. CRESTONE is now open and enrolling patients at approximately 30 clinical trial sites across three countries. Through the "just-in-time" clinical site model in partnership with Caris Life Sciences, Tempus, and US Oncology, there are over 400 available sites that can be activated within the CRESTONE study.
Corporate

Strengthened corporate leadership. During the third quarter, the company announced Valerie Malyvanh Jansen, MD, PhD, as the company’s first Chief Medical Officer. Dr. Jansen was promoted from her prior role as Vice President, Clinical Development.
Upcoming Milestones

Complete enrollment of the first 20 patients in Cohort 1 of the CRESTONE study in mid-2022
Present initial clinical data from approximately 10 patients from Cohort 1 of the CRESTONE study treated with seribantumab at 3 grams weekly at a major medical meeting in mid-2022
Third Quarter 2021 Financial Results

As of September 30, 2021, the Company had cash and cash equivalents totaling $155.2 million, which is expected to fund current operations into the second quarter of 2023.

Research and development expenses for the third quarter 2021 were $9.3 million, compared to $2.6 million for the third quarter 2020. The increase in R&D expense was primarily related to an increase in manufacturing and clinical trial expenses associated with the CRESTONE study.

General and administrative expenses for the third quarter 2021 were $3.0 million, compared to $0.5 million for the third quarter 2020. The increase in G&A expense was primarily related to personnel costs, professional services and consulting, and other administrative costs.

Net loss for the third quarter 2021 was $12.3 million, compared to $3.0 million for the third quarter 2020.

About Seribantumab and NRG1 Gene Fusions

Seribantumab is a fully human IgG2 monoclonal antibody that binds to human epidermal growth factor receptor 3 (HER3). HER3 is traditionally activated through binding of its primary ligand, neuregulin-1 (NRG1). The NRG1 gene fusion is a rare genomic alteration that combines NRG1 with another partner protein to create chimeric NRG1 "fusion proteins". The NRG1 fusion protein is often also able to activate the HER3 pathway, leading to unregulated cell growth and proliferation. Importantly, NRG1 gene fusions are predominantly mutually exclusive with other known genomic driver mutations and are considered a unique oncogenic driver event associated with tumor cell survival.

NRG1 fusions have been identified in a variety of solid tumors, including lung, pancreatic, gallbladder, breast, ovarian, colorectal, neuroendocrine, cholangiocarcinomas, and sarcomas. In preclinical experiments, seribantumab prevented the activation of HER3 signaling in cells that harbor an NRG1 gene fusion and destabilized the entire ERBB family signaling pathway including the activation of HER2, EGFR, and HER4. In addition to extensive nonclinical characterization and testing, seribantumab has been administered to over 800 patients across twelve Phase 1 and 2 studies, both as a monotherapy and in combination with various anti-cancer therapies. Seribantumab is currently being evaluated in the Phase 2 CRESTONE study for patients with solid tumors of any origin that have an NRG1 fusion.

About the CRESTONE Study

Clinical Study of Response to Seribantumab in Tumors with Neuregulin-1 (NRG1) Fusions. CRESTONE is a Phase 2 tumor-agnostic "basket trial" of seribantumab in patients with solid tumors that harbor an NRG1 fusion and have progressed after at least one prior line of standard therapy. The primary objective of the study is to describe the anti-tumor activity and safety of seribantumab as a monotherapy specifically in patients whose solid tumor is uniquely driven by an NRG1 gene fusion. CRESTONE offers a clinical trial opportunity for patients with advanced solid tumors who have not responded or are no longer responding to treatment. Patients are encouraged to talk to their doctor about genomic testing of their tumor. CRESTONE is open and enrolling today in the United States, Australia, and Canada. For more information visit www.NRG1fusion.com.

On November 12, 2021 Regeneron Pharmaceuticals, Inc. (NASDAQ: REGN) reported that its Board of Directors authorized a share repurchase program of up to $3 billion of the Company’s outstanding common stock (Press release, Regeneron, NOV 12, 2021, View Source [SID1234595406]).

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!

"With the strength of our balance sheet and our business, we see this as an opportunity to continue to invest in Regeneron," said Robert E. Landry, Executive Vice President, Finance and Chief Financial Officer of Regeneron. "This share repurchase program is part of our broader capital allocation strategy to maximize shareholder value for years to come."

Repurchases may be made from time to time at management’s discretion through a variety of methods, such as open-market transactions (including pre-set trading plans), privately negotiated transactions, accelerated share repurchases, and other transactions in accordance with applicable securities laws. The program has no time limit and can be discontinued at any time. No shares have been repurchased under the program to date. There can be no assurance as to the timing or number of shares of any repurchases. As of November 12, 2021, $1.8 million remained available for share repurchases under the prior $1.5 billion share repurchase program authorized in January 2021.

On November 12, 2021 Ocuphire Pharma, Inc. (Nasdaq: OCUP), a clinical-stage ophthalmic biopharmaceutical company focused on developing and commercializing therapies for the treatment of refractive and retinal eye disorders, reported financial results for the third quarter of 2021 and provided a corporate update (Press release, Ocuphire Pharma, NOV 12, 2021, View Source [SID1234595444]).

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 third quarter marked continued progress across our late-stage clinical programs and opportunities for multiple data presentations at major medical meetings," said Mina Sooch, MBA, President and CEO of Ocuphire Pharma. "We have already achieved two successful clinical trials for Nyxol. In reversal of mydriasis (RM), we reported positive results in a Phase 3 trial and are on track to initiate the second Phase 3 trial before year end. In presbyopia, we reported positive results in a Phase 2 clinical trial. We are also delighted to see the early US regulatory approval of Allergan’s VUITYTM eye drops, the first pharmaceutical therapy for the large presbyopia market."

"We are also very pleased to see a growing body of supportive research for our Phase 2 oral drug candidate, APX3330, which inhibits known pro-angiogenic and pro-inflammatory pathways. As a highly differentiated, first-in-class and orally-delivered therapy, we believe APX3330 will be an important source of potential value creation with the opportunity to broadly address the unmet global clinical need in diabetic retinopathy and treatment burden in other retinal diseases."

"This week marks Ocuphire’s one-year anniversary of public trading on the Nasdaq and we are proud to have achieved so many important clinical and business milestones in that time. We thank our clinical trial participants and investigators for their continued support. Looking ahead, we believe 2022 is shaping up to be an even more exciting and catalyst-rich year to build significant value for our company and our shareholders, with cash on hand that provides runway into late 2022 to achieve these milestones."

Key Anticipated Future Milestones

Reversal of Mydriasis (RM): Initiate second Phase 3 (MIRA-3) registration trial in subjects 12 and older and a small pediatric trial in subjects ages 3 to 11 (MIRA-4) in the fourth quarter of 2021 investigating Nyxol with results expected in early 2022; Planning to file NDA submission with FDA for Nyxol in RM indication in late 2022
Presbyopia: Initiate Phase 3 program (VEGA-2) in first half of 2022 investigating Nyxol and Low-Dose Pilocarpine (LDP)
Night Vision Disturbances (NVD): Top-line data expected in early 2022 from Phase 3 (LYNX-1) registration trial investigating Nyxol
Diabetic Retinopathy (DR) and Diabetic Macular Edema (DME): Top-line data expected in the second half of 2022 for the randomized, well-controlled Phase 2 (ZETA-1) trial investigating APX3330
Third Quarter and Recent Business Highlights

Presentations and Publications

In November, clinical data on Nyxol and APX3330 were accepted for presentation at poster sessions at the American Academy of Ophthalmology (AAO) 2021 annual meeting to take place in New Orleans, November 12 – 15. In addition, Ocuphire presented new data on improvement in intermediate vision and Snellen equivalent near vision at the [email protected] 2021 conference on November 11. Ocuphire was one of two companies presenting clinical data for presbyopia at this meeting.
In October, the Company announced the publication of a review article within the Special Issue "Advances in Molecular Activity of Potential Drugs" of the International Journal of Molecular Sciences, focused on how novel inhibitors of APE1/Ref-1 such as APX3330 may have the potential to improve disease outcomes for retinal disease patients. The article underscores the role of the APE1/Ref-1 protein in pro-angiogenic pathways associated with neovascular eye disease including diabetic retinal diseases and age-related macular degeneration. It can be accessed online at the following link: Inhibition of APE1/Ref-1 for Neovascular Eye Disease: From Biology to Therapy.
In October, the Company announced the publication of a review article in Cells titled "Potential Therapeutic Candidates for Age-Related Macular Degeneration" noting the potential of APX3330 (referred to as "E3330") for the treatment of age-related macular degeneration (AMD). Because APE1/Ref-1 has been shown to contribute to retinal angiogenesis, the authors conclude that APE1/Ref-1 inhibitors such as APX3330 could inhibit the abnormal blood vessel formation seen in AMD by reducing retinal endothelial cell proliferation, migration, and tube formation. The article can be accessed online at the following link: Potential Therapeutic Candidates for Age-Related Macular Degeneration (AMD).
In October, Michael J. Allingham, MD, PhD presented at the 39th Annual Scientific Meeting of the American Society of Retina Specialists (ASRS) (Diabetic Retinopathy 1 Symposium), highlighting the favorable safety and tolerability data for APX3330 in over 300 healthy volunteers and cancer/inflammation disease patients across 11 Phase 1 and Phase 2 studies. Also, Mina Sooch, CEO, presented APX3330 history and the design of the ongoing Phase 2 trial in DR at the OIS Retina Innovation [email protected].
In July, the Company announced publication in the Journal of Cellular Signaling featuring Ocuphire’s novel oral Ref-1 inhibitor APX3330 in Phase 2 trial for the treatment of retinal disease which highlighted the favorable safety profile of APX3330 and its unique anti-angiogenic and anti-inflammatory mechanism of action properties relevant to a broad range of retinal diseases.
In July, at the 2021 American Society of Cataract and Refractive Surgery (ASCRS) Annual Meeting, Dr. Jay S. Pepose, Medical Advisor and Board Director, presented papers featuring positive results for Nyxol in two studies: Phase 2 Presbyopia (VEGA-1) and Phase 3 Reversal of Mydriasis (MIRA-2). The Phase 3 MIRA-2 data presentation at ASCRS won the Best Paper of the Session.
In July, Mina Sooch, CEO, participated in the presbyopia drug therapy panel at the [email protected] 2021 held on July 22nd and in the Eye on Innovation panel at the Virtual Salon Series held on July 28th.
Intellectual Property

U.S. Patent and Trademark Office issued patent no. 11,160,770 "Compounds, compositions and methods for treating oxidative DNA damage disorders" which provides protection for APX2009 and other APX pipeline candidates.
Third Quarter and Year-To-Date 2021 Financial Highlights

As of September 30, 2021, the Company had cash and cash equivalents of approximately $22.2 million. Net cash used in operating activities for the nine months ended September 30, 2021 was $13.7 million.

Collaborations revenue was $0.5 million and $0.6 million for the three months and nine months ended September 30, 2021, respectively. Revenue during the periods was derived from the license agreements with Biosense Global, LLC and Processa Pharmaceuticals, Inc. related to certain technology transfers. There was no collaborations revenue recognized during the comparable prior year periods.

General and administrative expenses for the three months and nine months ended September 30, 2021 were $1.6 million and $6.7 million, respectively, compared to $0.6 million and $1.5 million for the comparable periods in 2020, respectively. The increases in the current periods were primarily attributable to administrative employee headcount, stock-based compensation, professional services, insurance, legal and settlement costs, and costs associated with operating as a public company subsequent to the reverse merger.

Research and development expenses for the three months and nine months ended September 30, 2021 were $3.1 million and $10.4 million, respectively, compared to $1.4 million and $2.3 million for the comparable periods in 2020, respectively. In the current periods, the increases were primarily attributable to new clinical trials and manufacturing activities for Nyxol and APX3330 as well as regulatory, preclinical and other development activities.

The loss from operations for the three and nine months ended September 30, 2021 was $4.2 million and $16.6 million, respectively, compared to $1.9 million and $5.9 million for the three and nine months ended September 30, 2020, respectively.

There was a non-cash expense of $33.8 million related to fair value change in warrant liabilities recorded for the nine months ended September 30, 2021 compared to a benefit of $0.2 million recorded for the nine months ended September 30, 2020 related to premium conversion derivatives. The reported losses also included non-cash stock-based compensation expense of $0.5 million and $1.4 million during the three and nine months ended September 30, 2021, respectively, and $0.6 million and $1.0 million during the three and nine months ended September 30, 2020, respectively.

For further details on Ocuphire’s financial results refer to the Company’s Quarterly Report on Form 10-Q for the quarter ended September 30, 2021, as filed with the Securities and Exchange Commission.

On November 12, 2021 SQZ Biotechnologies (NYSE: SQZ), focused on unlocking the full potential of cell therapies for multiple therapeutic areas, reported that new SQZ AAC and eAPC preclinical research describing the robust potential of these platforms to treat cancer, including data demonstrating synergistic activity when combined with chemotherapy (Press release, SQZ Biotech, NOV 12, 2021, View Source [SID1234595461]). The company also presented new research on the development of enhanced tumor infiltrating lymphocytes (TILs) that show increased potency in the absence of exogenous cytokine (IL-2) support. The data was presented at the 36th Annual Meeting of the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) being held November 10-14, 2021, in Washington, D.C. and virtually.

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!

"Our presentations at SITC (Free SITC Whitepaper) provide compelling new preclinical data on the multiple biologically diverse, directed immunity approaches that we are pursuing for cancer therapies," said Howard Bernstein, M.D., Ph.D., Chief Scientific Officer at SQZ Biotechnologies. "Our AAC and eAPC platform work provides translational insights that are relevant to clinical development, including combination chemotherapy and potential expansion to broader patient populations and tumor types."

"We are also excited to present initial preclinical results on enhanced tumor infiltrating lymphocytes, highlighting a potential future therapeutic avenue," said Jonathan Gilbert, Ph.D., Vice President and Head of Exploratory Research, SQZ Biotechnologies. "Working with tumor reactive TILs provided by AgonOx, Inc., we developed mRNA engineered TILs that can proliferate and kill matched patient tumor cells in the absence of exogenous IL-2 cytokine support. Engineered TILs may enable the removal of toxic preconditioning and systemic IL-2 use with TIL therapies, making them more broadly applicable to patients."

Major Findings from Preclinical Research

Poster #156: RBC-Derived, Activating Antigen Carriers (SQZ AACs) Prime Potent T Cell Responses and Drive Tumor Regression In Vivo

SQZ Activating Antigen Carriers (AAC) were derived from red blood cells (RBCs) and engineered to direct tumor-specific antigens and adjuvant to endogenous professional APCs, which subsequently activated T cell responses in vivo
In TC-1 tumor bearing mice, a model of HPV16+ cancers, AACs demonstrated a synergistic therapeutic effect in combination with cisplatin, a common chemotherapy used in many clinical settings
Median survival of mice increased in all combination treatment cohorts compared to single agent cisplatin or ACC treatment
Poster #211: SQZ eAPCs Generated from PBMCs by Delivery of Multiple mRNAs Encoding for Antigens, Costimulatory Proteins, and Engineered Cytokines

SQZ Enhanced Antigen Presenting Cells (eAPC) derived from peripheral blood mononuclear cells (PBMCs) and engineered with various mRNA encoding for multiple target antigens and immuno-stimulation signals, including CD86 and membrane bound IL-2 and IL-12, generated robust T cell responses in human in-vitro models
HPV16-encoding mRNA delivery to PBMCs stimulated CD8+ T cells across a range of HLA haplotypes, supporting future eAPC clinical development in broad HPV16+ patient populations
eAPC data highlights the potential to expand the therapeutic impact across tumor types by changing the antigen-encoding mRNA
Poster #165: Generating Enhanced Tumor Infiltrating Lymphocytes through Microfluidic Cell Squeezing

Cell Squeeze delivery of mRNA encoding membrane bound IL-2 (mbIL2) and IL-12 (mbIL12) into expanded tumor reactive CD8 human tumor infiltrating lymphocytes (TILs) from AgonOx* (AGX-148) demonstrated high levels of membrane-bound cytokine expression in vitro
Enhanced TILs proliferated independent of exogenous IL-2 and demonstrated improved granzyme B levels, illustrating the potential to eliminate systemic IL-2 administration in the clinical setting.
In an in vitro co-culture model with matched human melanoma cells, enhanced TILs demonstrated increased tumor killing as compared to un-modified TILs
* AgonOx, Inc. is a biotechnology company with a close alignment with the Earle A. Chiles Research Institute at the Providence Cancer Institute in Portland, OR.