On November 9, 2021 aTyr Pharma, Inc. (Nasdaq: LIFE), a biotherapeutics company engaged in the discovery and development of innovative medicines based on novel biological pathways, reported a poster presentation at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) Annual Meeting, which is being held November 10 – 14, 2021 in Washington, DC, and virtually (Press release, aTyr Pharma, NOV 9, 2021, View Source [SID1234594984]). The full text of the corresponding abstract is available on the SITC (Free SITC Whitepaper) website. The poster will be available for browsing on the SITC (Free SITC Whitepaper) website starting Friday, November 12 at 7:00 a.m. ET through Sunday, November 14 at 5:00 p.m. ET.

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The poster presents preclinical findings for ATYR2810, providing key insights into its mechanism of action that will help support the clinical development of ATYR2810, including a Phase 1 study in cancer next year. ATYR2810, an anti-Neuropilin-2 (NRP2) monoclonal antibody that blocks NRP2’s VEGF-induced signaling axis, was developed from aTyr’s research platform focused on targeting human disease pathways associated with extracellular tRNA synthetases. This work details the effects of ATYR2810 on tumor associated macrophages (TAMs) differentiated from human triple-negative breast cancer tumor cells. Treatment with ATYR2810 was shown to decrease the suppressive capabilities of TAMs against T cells compared to untreated TAMs. Furthermore, TAMs treated with ATYR2810 showed a decrease in ZEB1 gene expression, which is a master transcription factor regulating epithelial-mesenchymal transition (EMT), a process that is of great importance in regulating tumor growth, progression and metastatic cascade as well as being implicated in tumor evasion of the immune system. These results suggest that ATYR2810 may be able to treat cancer by targeting tumor immune avoidance mechanisms as well as regulating EMT.

Details of the poster and corresponding abstract are as follows:

Title: ATYR2810, an anti-NRP2 monoclonal antibody, targets tumor associated macrophages
Authors: Samantha Tyler, Michaela Ferrer, Erik Escobedo, Kaitlyn Rauch, Sofia Klopp-Savino, Justin Rahman, Zhiwen Xu, Esther Chong, Suzanne Paz, Leslie Nangle. aTyr Pharma, San Diego, CA.
Abstract Number: 699
Date and Time: November 12 – 14, 2021 from 7:00AM – 5:00PM ET

"We are pleased to demonstrate, for the first time, modulation of key cells associated with suppressing T cell-mediated anti-tumor responses in the tumor microenvironment as a result of treatment with ATYR2810, aTyr’s IND candidate in preclinical development for aggressive solid tumors where NRP2 is implicated," said Leslie Nangle, Ph.D., Vice President, Research at aTyr. "It is well known that TAMs suppress T cell activity and play an important role in the induction of EMT, contributing to therapy resistance and metastasis. As we and others have shown, these highly suppressive TAMs express high levels of NRP2. The ability of ATYR2810 to regulate EMT-related genes like ZEB1 in human TAMs and reduce their suppressive nature provides insight into the role of NRP2/VEGF signaling in TAMs. These findings advance our understanding of ATYR2810’s mechanism of action and the process by which it may inhibit tumor progression and disrupt immune evasion."

About ATYR2810

aTyr is developing ATYR2810 as a potential therapeutic for certain aggressive tumors where Neuropilin-2 (NRP2) is implicated. ATYR2810 is a fully humanized monoclonal antibody that is designed to specifically and functionally block the interaction between NRP2 and one of its primary ligands, VEGF. ATYR2810 is the first Investigational New Drug (IND) candidate to arise from aTyr’s in-house research program designing monoclonal antibodies to selectively target the NRP2 receptor and its associated signaling pathways. NRP2 is a cell surface receptor that is highly expressed in certain tumors, in the lymphatic system and on key immune cells implicated in cancer progression. Increased NRP2 expression is associated with worse outcomes in many cancers. Preclinical data suggest that ATYR2810 could be effective against certain types of solid tumors. ATYR2810 is currently undergoing IND-enabling studies.

On November 9, 2021 Pliant Therapeutics, Inc. (Nasdaq: PLRX) ("the Company"), a clinical stage biotechnology company focused on discovering and developing novel therapeutics for the treatment of fibrosis, reported third quarter 2021 financial results (Press release, Pliant Therapeutics, NOV 9, 2021, View Source [SID1234595036]).

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"The third quarter was productive for the company, highlighted by the interim data readout from our PET trial which exceeded our expectations, showing a dose response and achieving near target saturation of PLN-74809 at the higher doses," said Bernard Coulie, M.D., Ph.D., President and Chief Executive Officer of Pliant Therapeutics. "In addition to the positive data readout, our Phase 2a INTEGRIS-IPF and INTEGRIS-PSC programs are making great progress in enrollment, and, with the additional Phase 1b BAL doses, we continue to methodically de-risk the current and future clinical development of PLN-74809."

Third Quarter and Recent Highlights

Positive interim results from Phase 2a PET imaging clinical trial show αvβ6 target engagement up to 98% in the lungs of patients with idiopathic pulmonary fibrosis (IPF). The ongoing Phase 2a open-label PET imaging clinical trial is evaluating αvβ6 target engagement levels achieved by PLN-74809 across single-doses of 60, 120, 240 or 320 mg in up to 12 IPF patients. Interim results showed a dose response and a greater than 50% target engagement across all doses and established a model of the dose and plasma concentration response. Furthermore, these data support potential anti-fibrotic activity of PLN-74809 at the doses being evaluated in the ongoing Phase 2a INTEGRIS-IPF trial.

PLN-74809 Phase 2a trial in idiopathic pulmonary fibrosis (IPF) enrollment on track with topline data anticipated by mid-2022. INTEGRIS-IPF is a 12-week randomized, dose-ranging, double-blind, placebo-controlled trial evaluating the safety, tolerability and pharmacokinetics of PLN-74809 at doses of 40, 80 or 160 mg in IPF patients. Exploratory endpoints include quantitative lung fibrosis (QLF) imaging, pulmonary function tests as well as biomarkers. Enrollment is currently on track to be completed by the end of 2021 with topline data anticipated by mid-2022.

Data anticipated in the first quarter of 2022 from additional doses in the PLN-74809 Phase 1b proof-of-mechanism study evaluating inhibition of TGF-β signaling in the lungs of healthy volunteers. In a previously reported Phase 1b proof-of-mechanism study, 40 mg once-daily dosing of PLN-74809 inhibited activation of TGF-β, a key driver of fibrosis. Based on additional safety and pharmacokinetic data from the Phase 1a study, Pliant initiated an extension of the Phase 1b study. This study extension evaluates inhibition of TGF-b signaling at doses above 40 mg of PLN-74809. These data, coupled with the recently reported positive interim Phase 2a PET target engagement data, will provide important information about the relationship between PLN-74809 plasma exposure, target engagement, TGF-β signaling inhibition and potential antifibrotic activity across the dose range currently being tested in the INTEGRIS-IPF trial. Data from this Phase 1b study is anticipated in the first quarter of 2022.

PLN-74809 Phase 2a trial in primary sclerosing cholangitis (PSC) enrollment on track. INTEGRIS-PSC is a 12-week randomized, dose-ranging, double-blind, placebo-controlled trial evaluating the safety, tolerability, and pharmacokinetics PLN-74809 at doses of 40, 80 or 160 mg in PSC patients. Exploratory endpoints include fibrosis

biomarkers such as Pro-C3 and ELF, changes in ALP and liver imaging. Enrollment is currently anticipated to be completed by mid-2022.

Muscular Dystrophy and Oncology programs advancing towards IND. Early-stage integrin targeting programs focused on developing novel therapies in oncology and muscular dystrophies continue to advance towards IND. The muscular dystrophy program utilizes an antibody to improve muscle function through activation of an integrin compensatory mechanism. The oncology program focuses on increasing tumor sensitivity to checkpoint inhibitors through small molecule inhibition of αvβ8.

COVID-19 Preparedness
The Company continues to develop and maintain policies and procedures to enable us to operate safely and productively during the COVID-19 pandemic. The Company has experienced delays in clinical trial operations which have impacted and may further impact the expected timing of data readouts. The Company continues to work closely with clinical sites to continue site initiation and operation activities in compliance with study protocols while observing government and institutional guidelines.

Third Quarter 2021 Financial Results
•Research and development expenses were $21.1 million, as compared to $16.9 million for the prior-year quarter. The increase was due primarily to employee related expenses and higher costs related to the advancement of several programs and ongoing Phase 1/2 clinical trials.
•General and administrative expenses were $7.7 million, as compared to $4.6 million for the prior-year quarter. The increase was due to higher personnel-related and professional services expenses.
•Net loss of $27.0 million as compared to $16.5 million for the prior-year quarter due an overall increase in expense associated with our research and development programs as well as personnel-related costs.
•As of September 30, 2021, the Company had cash, cash equivalents and short-term investments of $221.0 million. The Company believes it has sufficient funds to meet its operating and capital requirements into 2023.

On November 9, 2021 Xencor reported Novartis terminated its rights to develop vibecotamab, a CD123 x CD3 blood cancer bispecific, which was part of a 2016 collaboration valued at $2.6 billion (Press release, Xencor, NOV 9, 2021, View Source [SID1234595329]).

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Since the collaboration was first forged, Novartis has slowly stepped away from the partnership. In 2019, the Swiss pharma giant backed away from developing XmAb13676, a CD20 x CD3 bispecific antibody, following a strategic pipeline reprioritization. Now, Novartis is terminating rights to the vibecotamab program, effective February 2022.

In 2019, shortly after Novartis dumped development rights to XmAb13676, the other asset was hit with a partial clinical hold by the U.S. Food and Drug Administration. The CD123 x CD3 blood cancer bispecific was assessed in a Phase I study for acute myeloid leukemia. Two patients in the trial died.

CD123 is a tumor-associated antigen overexpressed on the surface of some tumor cells. The CD3 complex is a group of proteins on the surface of T-cells. Multiple companies have taken this approach against leukemia, but results have been less than encouraging.

In 2016, Janssen and Genmab saw a hold placed on their CD123 x CD3 candidate for acute myeloid leukemia. Cellectis also caught a clinical hold on two Phase I trials of its CD123 asset, UCART123.

Xencor announced Novartis’ decision in its third quarter financial report. The company stated that it would continue the ongoing study of vibecotamab, but it no longer intends further internal development of the drug once it is complete.

There is still hope that something from the partnership with Novartis could be salvaged through the development of another asset. Earlier this year, the larger company selected a candidate to develop. The outcome for that study is still off in the future.

Although the partnership with Novartis has taken a significant blow, Xencor could see fruit from a collaboration with Janssen. In October, the two companies entered into a partnership to advance the development of plamotamab and XmAb CD28 bispecific antibody combinations to treat patients with B-cell malignancies. Under terms of that deal, Janssen secured exclusive worldwide development and commercial rights to plamotamab, an investigational tumor-targeted XmAb bispecific antibody, currently in Phase I clinical development as a potential treatment for patients with CD20-expressing hematologic malignancies.

Xencor is paying 20% of costs, including those for a subcutaneous formulation study that is expected to enter clinical studies in 2022. In the meantime, Xencor will continue, at its own expense, the combination study of plamotamab, tafasitamab and lenalidomide.

Xencor is also partnered with Bristol Myers Squibb on the development of potential antibody treatment for COVID-19. The two companies will advance the development of Xencor’s Xtend Fc technology.

On November 9, 2021 Selecta Biosciences, Inc. (NASDAQ: SELB), a biotechnology company leveraging its clinically validated ImmTOR platform to develop tolerogenic therapies that selectively mitigate unwanted immune responses, reported financial results for the third quarter ended September 30, 2021 and provided a business update (Press release, Selecta Biosciences, NOV 9, 2021, View Source [SID1234594803]).

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"The third quarter of 2021 was filled with many significant advancements that further validated the value and breadth of our innovative ImmTOR platform, including important milestones across our pipeline and the establishment of numerous collaborations that will continue to propel us forward in the year ahead," said Carsten Brunn, Ph.D., president and chief executive officer of Selecta. "We recently presented topline data from the empty AAV8 capsid study, SEL-399 in healthy volunteers. We believe this pioneering proof-of-concept study showed for the first time ImmTOR’s potential to address one of the biggest limitations in gene therapy: preventing the formation of anti-AAV8 neutralizing antibodies after ImmTOR treatment with AAVs and enabling re-dosing of life-saving gene therapies. We are excited to build on these exciting findings, which will inform our clinical development strategy and bring hope to those patients suffering from monogenic disease. We continue to prosecute our clinical pipeline, execute value accretive business development with world class partners and add talent and depth to our leadership team."

Recent Highlights and Anticipated Upcoming Milestones:
Enzyme Therapies:

SEL-212 for chronic refractory gout: Enrollment for the Phase 3 DISSOLVE clinical program for the treatment of chronic refractory gout, which was licensed to Sobi, is progressing as planned.
Topline data is expected in the second half of 2022.
ImmTOR with IgA1 protease for IgA nephropathy: Immunoglobulin A nephropathy (IgAN) is a leading cause of chronic kidney disease (CKD) and renal failure. Current treatments fail to address the root cause of the disease.
Investigational New Drug, or IND, enabling studies are underway. Selecta expects to file an IND in IgA nephropathy in 2022 and will provide additional updates.
Gene Therapies:

First-in-human trial of SEL-399: In collaboration with AskBio, Selecta initiated the first-in-human, dose-escalation trial of SEL-399, an adeno-associated viral serotype 8 (AAV8) empty vector capsid (EMC-101) containing no DNA combined with ImmTOR. The key objective was to determine the dose regimen of ImmTOR to effectively mitigate the formation of antibodies to AAV8 capsids used in gene therapies. Data was released on November 8, 2021. Key findings included:
No Serious Adverse Events were reported. All treatment-related adverse events were expected for ImmTOR, readily monitorable, and transient
At 30 days 6 of 6 or 100% of subjects that received 0.3 mg/kg of ImmTOR exhibited an anti-AAV8 neutralizing antibody titer of 1:25 or less. 4 of 6 or 67% of subjects at this dose had a titer of 1:5 or less
At 30 days 6 of 9 or 67% of subjects that received 0.15 mg/kg of ImmTOR exhibited an anti-AAV8 neutralizing antibody titer of 1:25 or less. 2 of 9 or 22% of subjects at this dose had a titer of 1:5 or less
At 90 days 2 of 6 subjects in the 0.3 mg/kg cohort were observed to have sustained control of neutralizing antibodies with titers of 1:25 or less
Consistent with preclinical data, we observed that the single dose ImmTOR cohorts saw delayed formation of neutralizing antibodies eventually reaching similar median levels of neutralizing antibodies to the control group by day 90
While most subjects treated with ImmTOR showed increases in antibody titers by Day 90, preclinical studies in mice and nonhuman primates indicate that if antibodies can be controlled at Day 30, we can maintain control with additional two monthly doses of ImmTOR.

SEL-302 for methylmalonic acidemia (MMA): IND filed for SEL-302 (MMA-101 in combination with ImmTOR), for the treatment of MMA, a rare metabolic disease in which the body cannot break down certain proteins and fats.
IND filed in Q3 2021, 30-day FDA review period has expired.
FDA has orally communicated they are still considering certain aspects of the submission related to chemistry, manufacturing and control, or CMC.
Formal FDA decision on IND expected by the end of November.
SEL-313 for ornithine transcarbamylase deficiency (OTC deficiency): Selecta’s proprietary gene therapy product candidate, SEL-313, is being developed to treat OTC deficiency, a rare genetic urea cycle disorder that causes ammonia to accumulate in the blood due to mutations in the OTC gene.
SEL-313 is currently in preclinical development and a clinical trial application, or CTA, and/or IND filing are expected in 2022.
Restoring Self-Tolerance in Autoimmune Diseases:

Selecta continues IND-enabling work on an ImmTOR-based approach to treating primary biliary cholangitis (PBC) and expects to file an IND in PBC in the second half of 2022.
Corporate Updates:

Strategic Collaborations:
Gene Therapies
Takeda Pharmaceutical Company Limited ("Takeda"): Strategic licensing agreement to develop next-generation gene therapies in two lysosomal storage disorders. The collaboration leverages Selecta ImmTOR platform to enable redosing of transformative therapies.
Genovis: Strategic licensing agreement to advance a next-generation IgG protease. This partnership leverages Genovis’ proprietary and differentiated immunoglobulin G (IgG) protease, IdeXork (Xork), and Selecta’s ImmTOR platform to enable the dosing of transformative gene therapies in patients with pre-existing adeno-associated virus (AAV) immunity and treat certain IgG-mediated autoimmune diseases. Xork shows low crossreactivity to pre-existing antibodies in human sera. The combination of Xork with ImmTOR has the potential to address two of the biggest immunological challenges to gene therapy – expanding access to gene therapies by overcoming pre-existing antibodies to AAV and enabling vector re-dosing.
Enzymes
Ginkgo Bioworks ("Ginkgo"): Partnership to design novel enzymes and proteins with transformative therapeutic potential to advance treatments for orphan and rare diseases. This partnership leverages Ginkgo’s cell programing platform and Selecta’s ImmTOR platform to create transformative biologic and enzymatic therapies.
Autoimmune
Cyrus Biotechnology ("Cyrus"): Established protein engineering collaboration combining Selecta’s ImmTOR platform with Cyrus’ ability to radically redesign protein therapeutics. The lead program in the collaboration is a proprietary interleukin-2 (IL-2) protein agonist designed to selectively promote expansion of regulatory T cells (Treg) for the treatment of patients with autoimmune diseases and other deleterious immune conditions. The combination of ImmTOR with a Treg-selective IL-2 agonist has the potential to be a best-in-class therapeutic profile.
Leadership Expansion:
Kevin Tan was appointed as chief financial officer. Mr. Tan brings deep financial expertise and experience in the gene therapy and rare disease landscape. His impressive track record in capital management and financings, in both the biotech and investment sectors, will be invaluable as Selecta continues to pursue new partnership opportunities and advance multiple assets through the clinic.
Matthew Bartholomae was appointed as General Counsel, Board Secretary and transitioned from his previous role at Selecta as Associate General Counsel, Board Secretary.
Third Quarter 2021 Financial Results:

Cash Position: Selecta had $140.0 million in cash, cash equivalents, marketable securities, and restricted cash as of September 30, 2021, which compares to cash, cash equivalents, and restricted cash of $140.1 million as of December 31, 2020. Selecta believes its available cash, cash equivalents, marketable securities, and restricted cash will be sufficient to meet its operating requirements into the second quarter of 2023.

Net cash used in operating activities was $28.9 million for the nine months ended September 30, 2021, as compared to $42.1 million of cash provided by operating activities for the same period in 2020.
Revenue: Revenue for the third quarter of 2021 was $24.4 million, compared to $4.6 million for the same period in 2020. Revenue of $24.3 million was recognized under the license agreement with Sobi resulting from the shipment of clinical supply and the reimbursement of costs incurred for the Phase 3 DISSOLVE clinical program. The significant revenue increase is the result of the continued enrollment of the Phase 3 DISSOLVE clinical program that was initiated in the third quarter of 2020. Additionally, during the third quarter, Selecta recognized $0.2 million for shipments under the license agreement with Sarepta.

Research and Development Expenses: Research and development expenses for the third quarter 2021 were $21.0 million, which compares with $14.0 million for the same period in 2020. During the quarter ended September 30, 2021, there was an increase in expenses incurred for preclinical programs, salaries, headcount, and AskBio collaboration costs.

General and Administrative Expenses: General and administrative expenses for the third quarter 2021 were $5.4 million, which compares with $4.4 million for the same period in 2020. The increase in costs was primarily the result of salaries, professional fees, and stock compensation expenses.

Net loss: For the third quarter 2021, Selecta reported net loss of $17.9 million, or net loss per share of $0.16, compared to a net loss of $9.7 million, or net loss per share of $0.09 for the same period in 2020.

Conference Call and Webcast Reminder
Selecta management will host a conference call at 8:30 AM ET today to provide a corporate update and review the company’s third quarter 2021 financial results. Individuals may participate in the live call via telephone by dialing (844) 845-4170 (domestic) or (412) 717-9621 (international) and may access a teleconference replay for one week by dialing (877) 344-7529 (domestic) or (412) 317-0088 (international) and using confirmation code 10147803. Investors and the public can access the live and archived webcast of this call and a copy of the presentation via the Investors & Media section of the company’s website, www.selectabio.com.

On November 9, 2021 ERYTECH Pharma (Nasdaq & Euronext: ERYP), a clinical-stage biopharmaceutical company developing innovative therapies by encapsulating therapeutic drug substances inside red blood cells, reported that its CEO, Gil Beyen, will participate in a fireside chat at the 12th Annual Jefferies London Healthcare Conference and invites investors to participate in one-on-one meetings both in-person on Tuesday and Wednesday, November 16th/17th or virtually on Thursday and Friday, November 18th/19th (Press release, ERYtech Pharma, NOV 9, 2021, View Source [SID1234594838]).

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