On March 25, 2021 InflaRx (Nasdaq: IFRX), a clinical-stage biopharmaceutical company developing anti-inflammatory therapeutics by targeting the complement system, reported financial results for the year ended December 31, 2020 (Press release, InflaRx, MAR 25, 2021, View Source [SID1234577129]).

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Prof. Niels C. Riedemann, Chief Executive Officer and Founder of InflaRx, commented: "The year 2020 was a challenging one for all of us dealing with a pandemic. As a physician and scientist, it has been extremely rewarding to see how quickly effective vaccines have been developed and are already in the arms of thousands of people. However, we continue to see a need for novel treatments for COVID-19 and similar future viral diseases. We are happy to be evaluating vilobelimab as a potential treatment to help severe COVID-19 patients and look forward to seeing those results, as well as results from ongoing trials in other disease areas, later this year."

Prof. Riedemann continued: "We have submitted as planned a Special Protocol Assessment to the FDA to reach agreement on the path forward for our phase III plans with vilobelimab in hidradenitis suppurativa. We were excited to announce a new area of clinical development – oncology – and are on track to start our first cancer trial with vilobelimab in cutaneous squamous cell carcinoma in the second quarter of this year. I am also pleased that our team recently completed a $75 million public offering, further strengthening our cash position and putting us on a firm financial footing to advance vilobelimab in a number of indications. We look forward to reporting our progress in the months ahead."

Recent Highlights and R&D Update

Issue of Share Capital
On March 1, 2021, InflaRx announced the closing of a public offering of common shares pursuant to which the Company sold 15,000,000 common shares and warrants to purchase up to 15,000,000 common shares. The common shares were sold at a price to the public of $5.00 per share. For each common share purchased, an investor also received a warrant to purchase a common share at an exercise price of $5.80. The warrants are exercisable immediately and have a term of up to one year. The gross proceeds from this offering were $75.0 million (€61.6 million), before deducting the $4.5 million (€3.7 million) underwriting discount and other estimated offering expenses of approximately $0.5 million (€0.5 million) and excluding the exercise of any warrants.

Vilobelimab for Hidradenitis Suppurativa (HS)
InflaRx has submitted a Special Protocol Assessment (SPA) to the Food & Drug Administration (FDA) for the planned Phase III program in HS in the first quarter of 2021. Details on the Phase III design will be provided once agreement has been reached with the FDA.

In Europe, as previously reported in 2020, InflaRx received scientific advice from the European Medicines Agency (EMA) about the European pathway for regulatory approval, including supporting the use of a new primary endpoint, the International Hidradenitis Suppurativa Severity Score ("IHS4"). The Company is working diligently to address the additional feedback received to achieve alignment with the US strategy for a global Phase III development program in HS.

New data supporting the continued development of vilobelimab in the treatment of HS were presented in February 2021 at the 10th Conference of the European Hidradenitis Suppurativa Foundation e.V. (EHSF). The data from the SHINE Phase II trial showed that significantly elevated baseline C5a levels occurred in HS patients versus healthy volunteers. Data also showed that vilobelimab dose-dependently suppressed C5a levels over time accompanied by the previously reported reduction in inflammatory lesion counts and scores.

Vilobelimab for Severe COVID-19
The Phase III part of the global Phase II/III trial evaluating vilobelimab in mechanically ventilated patients with COVID-19 was initiated in mid-September 2020, and recruitment is currently ongoing with sites open in several countries in Europe and Latin America. Additional countries are in the process of being added. The study is enrolling as planned with a total goal of 360 patients. A blinded interim analysis is planned after 180 patients, with a potential early stop of the trial for efficacy or futility. Topline data from the trial are expected to be available by the end 2021.

Vilobelimab for ANCA-associated Vasculitis (AAV)
InflaRx reported the completion of enrollment in the European Phase II IXCHANGE study of vilobelimab in AAV in Q1 2021. Topline data from the randomized, double-blind, placebo-controlled trial with 57 patients are expected by the end of 2021.

Vilobelimab is also being studied in the US phase II IXPLORE study in patients with AAV. The main objective of this randomized, double-blind, placebo-controlled study is to evaluate the safety of vilobelimab, as this is the first time the drug is being administered to patients with AAV in the US. Topline results are expected by mid-2021.

Vilobelimab in cutaneous squamous cell carcinoma (cSCC)
The Company has recently announced plans to initiate an open label, multicenter Phase II study evaluating vilobelimab alone and in combination with pembrolizumab in patients with PD-1 or PD-L1 inhibitor resistant/refractory locally advanced or metastatic cSCC.

The non-comparative two-stage multi-national Phase II trial is expected to start enrolling patients in Q2 2021 with sites in Europe, the US and other countries. The study will investigate two independent arms: vilobelimab alone and vilobelimab in combination with pembrolizumab. The main objectives of the trial are to assess antitumor activity and safety of vilobelimab monotherapy and to determine the maximum tolerated or recommended dose, safety and antitumor activity in the combination arm.

Vilobelimab in Pyoderma Gangraenosum
The Phase IIa open label trial continues to enroll patients in the higher dose groups. Promising initial data from the first five patients in the study were announced in 2020. Results from the higher dose groups are expected by the end of 2021.

Financial highlights 2020

Research and development expenses decreased by €18.9 million to €25.7 million in the year ended December 31, 2020 compared to the year ended December 31, 2019.

This decrease is attributable to lower CRO and CMO costs from clinical trials in the amount of €16.9 million due to the conclusion of the Phase IIb for HS in 2019, the expense of which was higher than 2020 costs associated with the new Phase II/III clinical trial in patients with COVID (2020: €4.9 million, 2019: nil) or other running trials like Phase II clinical program in patients with AAV, the Phase II clinical program in patients with PG, the preparation of a Phase II clinical program in patients cSCC or ongoing manufacturing activities for clinical trial related materials.

In addition there was a €1.8 million decrease in employee-related costs mainly caused by a €2.0 million decrease in expenses from non-cash share-based compensation.

General and administrative expenses decreased by €4.0 million to €8.5 million for the year ended December 31, 2020, from €12.5 million for the year ended December 31, 2019. This decrease is primarily attributable to a €3.8 million decrease in expenses from non-cash share-based compensation. Legal, consulting and audit fees and other expenses decreased by €0.6 million to €1.6 million for the year ended December 31, 2020, from €2.2 million for the year ended December 31, 2019, which decrease is mainly attributable to lower consulting and travel costs. The increase of other expenses by €0.2 million is primarily related to higher D&O insurance cost.

Net financial result decreased by €3.6 million in the year ended December 31, 2020 compared to the year ended December 31, 2019. This decrease is mainly attributable to (a) higher foreign exchange losses, which increased by €1.7 million and (b) lower interest on marketable securities, which decreased by €2.0 million.

Net loss for the year 2020 was €34.0 million or €1.3 per common share, compared to €53.3 million or €2.1 per common share for the year 2019. On December 31, 2020, the Company’s total funds available were approximately €81.4 million, composed of cash and cash equivalents (€26.0 million) and financial assets (€55.4 million).

Net cash used in operating activities decreased to €36.5 million in the year ended December 31, 2020, from €43.2 million in the year ended December 31, 2019, mainly due to the decrease of research and development expenditures and lower personnel costs, excluding stock-based compensation.

Additional information regarding these results and other relevant information is included in the notes to the financial statements as of December 31, 2020 in "ITEM 18. Financial statements," which is included in InflaRx’s Annual Report on Form 20-F as filed with the US Securities and Exchange Commission.

InflaRx N.V. and subsidiaries
About vilobelimab:

Vilobelimab is a first-in-class monoclonal anti-human complement factor C5a antibody, which highly and effectively blocks the biological activity of C5a and demonstrates high selectivity towards its target in human blood. Thus, vilobelimab leaves the formation of the membrane attack complex (C5b-9) intact as an important defense mechanism, which is not the case for molecules blocking the cleavage of C5. Vilobelimab has been demonstrated to control the inflammatory response driven tissue and organ damage by specifically blocking C5a as a key "amplifier" of this response in pre-clinical studies. Vilobelimab is believed to be the first monoclonal anti-C5a antibody introduced into clinical development. Approximately 300 people have been treated with vilobelimab in clinical trials, and the antibody has been shown to be well tolerated. Vilobelimab is currently being developed for various indications, including Hidradenitis Suppurativa, ANCA-associated vasculitis, Pyoderma Gangraenosum, Cutaneous Squamous Cell Carcinoma and severe COVID‑19.

On March 25, 2021 Black Diamond Therapeutics, Inc. (Nasdaq: BDTX), a precision oncology medicine company pioneering the discovery and development of small molecule, tumor-agnostic therapies, reported financial results for the fourth quarter and full year ended December 31, 2019, while providing a corporate update (Press release, Black Diamond Therapeutics, MAR 25, 2021, View Source [SID1234577128]).

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"Black Diamond has achieved important scientific, clinical, and operational milestones over the past year," said David M. Epstein, Ph.D., President and CEO. "Our IND for our lead product candidate, BDTX-189, was allowed in December and we have initiated our Phase 1/2 clinical trial. We believe the $316 million raised since November, including via our initial public offering, will enable us not only to execute on the clinical development of BDTX-189, but also to continue to invest in our proprietary MAP platform, and to progress our early stage pipeline of small molecule, tumor-agnostic precision medicine programs."

2019 Corporate Highlights

Advanced BDTX-189, Black Diamond’s mutation spectrum-selective, oral, irreversible small molecule inhibitor product candidate which targets cancer-causing driver mutations in human epidermal growth factor receptor 2 (HER2) and epidermal growth factor receptor (EGFR) that have not yet been drugged, to investigational new drug (IND) application submission in November 2019 and IND allowance by the U.S. Food and Drug Administration in December 2019.
Initiated a Phase 1/2 clinical trial of BDTX-189, which is actively enrolling and dosing patients in the Phase 1 portion.
— The Phase 1 portion of the trial will evaluate escalating doses of BDTX-189 and is designed to determine the recommended Phase 2 dose and to assess preliminary indications of anti-tumor activity. The Phase 2 portion will determine the objective response rate and duration of response in patients with solid tumors that have an allosteric HER2 mutation or EGFR or HER2 exon 20 insertion mutation determined using next-generation sequencing.
Continued to advance its program in glioblastoma (GBM) toward nominating a development candidate that targets a range of driver mutations in GBM and progress the Company’s other earlier stage programs derived from Black Diamond’s Mutation-Allostery-Pharmacology (MAP) platform.
— Black Diamond’s MAP platform is built on three central pillars – discover, reveal, and target. The Company uses population-level cancer genetic data obtained from all tumor types to identify potential families of mutations that occur within individual oncogenes and rank the mutations for potential oncogenicity. Black Diamond then uses its MAP platform to understand the mechanism for oncogenic activation and the Company’s team of experienced medicinal chemists then develops mutation spectrum-selective drugs for the identified targets.
Raised $85.0 million in an oversubscribed Series C financing round in November 2019 led by Boxer Capital of the Tavistock Group. Additional new investors Wellington Management Company, BVF Partners L.P., Deerfield Management, funds managed by Janus Henderson Investors, Casdin Capital, and Logos Capital joined existing investors Versant Ventures, New Enterprise Associates, RA Capital Management, Nextech Invest, Invus, Perceptive Advisors, City Hill Ventures, and Roche Venture Fund in the round.
Strengthened Black Diamond’s management team and Board of Directors in 2019 by adding Brent Hatzis-Schoch as Chief Operating Officer and General Counsel, Thomas (Tommy) Leggett as Chief Financial Officer, and Christopher D. Roberts, Ph.D., as Chief Scientific Officer, along with Samarth (Sam) Kulkarni, Ph.D., CEO of CRISPR Therapeutics AG, to its Board of Directors.
Recent Developments

In February 2020, Black Diamond completed an initial public offering pursuant to which it issued and sold 12,174,263 shares of common stock, including full exercise of the underwriters’ over-allotment option, resulting in gross proceeds of $231.3 million before deducting underwriting discounts and commissions and other offering expenses.
Financial Highlights

Black Diamond ended 2019 with $154.7 million in cash and cash equivalents compared to $51.7 million as of December 31, 2018. Net cash from financing activities for the year ended December 31, 2019 was $127.8 million compared to $52.3 million for the year ended December 31, 2018. Net cash used in operations was $24.7 million for the year ended December 31, 2019 compared to $8.5 million for the year ended December 31, 2018.
Net loss for the year ended December 31, 2019 was $35.3 million compared to $8.9 million for the year ended December 31, 2018.
Research and development (R&D) expenses were $21.8 million for the year ended December 31, 2019 compared to $7.0 million for the year ended December 31, 2018. The increase in R&D expenses was primarily related to increase in headcount, preclinical development, and IND filing of BDTX-189.
General and administrative (G&A) expenses were $7.6 million for the year ended December 31, 2019, compared to $2.0 million for the year ended December 31, 2018. The increase in G&A expenses was primarily due to an increase in personnel and other corporate-related costs.

On March 25, 2021 Cancer Genetics, Inc. (the "Company") (Nasdaq: CGIX), an emerging leader in novel drug discovery techniques, reported the results of its March 24, 2021 shareholder meeting to approve the upcoming merger with StemoniX, Inc. ("StemoniX") (Press release, Cancer Genetics, MAR 25, 2021, View Source [SID1234577127]).

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At a Special Meeting of Stockholders, CGI’s stockholders, upon the unanimous recommendation of the board of directors of CGI: (a) voted in favor of the issuance of shares of Common Stock, warrants and options pursuant to the Agreement and Plan of Merger and Reorganization, dated as of August 21, 2020, as amended, with StemoniX; (b) voted in favor of the amendment to the certificate of incorporation of CGI effecting a reverse stock split of the issued and authorized shares of Common Stock, at a ratio in the range from 1-for-2 to 1-for-10, with such specific ratio to be determined by the CGI board; (c) voted to approve the Cancer Genetics, Inc. 2021 Equity Incentive Plan and to authorize for issuance 4,500,000 shares of Common Stock thereunder; and (d) voted to approve on an advisory basis, the compensation that may be paid or become payable to CGI’s named executive officers in connection with the merger.

Chief Executive Officer of Cancer Genetics, Jay Roberts, stated, "The Cancer Genetics team is thankful for the participation and support of our shareholders for voting in favor of the merger with StemoniX. In addition, we are thankful to our management teams and board members from both Cancer Genetics and StemoniX for their effort in bringing the merger to this point. We are proud to be combining forces and we are prepared to execute on our business plan.

On March 25, 2021 Synlogic, Inc. (Nasdaq: SYBX), a clinical stage company bringing the transformative potential of synthetic biology to medicine, reported financial results for the fourth quarter and full year ended December 31, 2020, and provided an update on programs and progress (Press release, Synlogic, MAR 25, 2021, View Source [SID1234577116]).

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"2021 is an incredibly exciting year for the company. We now have demonstrated proof of mechanism in humans from both of our lead metabolic programs, Phenylketonuria (PKU) and Enteric Hyperoxaluria, and expect to have important clinical readouts in patients from both programs later this year," said Aoife Brennan, M.B. Ch.B., Synlogic’s President and Chief Executive Officer. "We believe there is significant unmet need in PKU and Enteric Hyperoxaluria and that our Synthetic Biotic medicines can address these and other metabolic diseases in ways not possible with other modalities."

"Enteric Hyperoxaluria is a historically underserved area in which dangerously high levels of urinary oxalate cause progressive kidney damage," said Richard Riese, M.D., Synlogic’s Chief Medical Officer. "Part A of the Phase 1 study of SYNB8802 in healthy volunteers demonstrates compelling levels of Urinary Oxalate lowering at a well-tolerated dose in Dietary Hyperoxaluria cohorts, and we are thrilled to be advancing this program."

Dr. Riese further stated, "We are also excited to continue to advance the SynPheny-1 Phase 2 study of SYNB1618 for the treatment of PKU, as well as the Phase 1 clinical study of SYNB1891 in solid tumors and lymphomas. Patient interest continues to be robust. We are looking forward to top line results from both trials later in 2021."

2020 Highlights & 2021 Priorities

The Metabolic Portfolio:

Progression of a proof-of-concept Phase 2 clinical trial of SYNB1618 for the treatment of Phenylketonuria (PKU), with data expected in the second half of 2021. SYNB1618 is an orally administered Synthetic Biotic medicine being developed as a potential treatment for PKU.

Synthetic Biotic medicines offer potential for a safe, tolerable, reversible and oral therapy, which reduces plasma Phe levels by consuming Phe in the GI tract.
SynPheny-1 is designed to evaluate plasma Phe lowering of a solid oral formulation of SYNB1618 in adult PKU patients who do not benefit from, or do not tolerate, existing therapies such as Kuvan or Palynziq.
SYNB1934, an evolved Synthetic Biotic medicine in the PKU portfolio, has progressed to IND enabling studies.
SYNB1934 consumes Phe in the GI tract and contains a high activity PAL enzyme developed using directed evolution from the SYNB1618 PAL enzyme.
SYNB1934 may offer additional Phe lowering capacity, or the ability to dose at lower levels, relative to SYNB1618.
Synlogic will provide full results of the SYNB1618 Phase 1 study of a solid oral formulation in healthy volunteers at the American College of Medical Genetics (ACMG) meeting in April 2021.
Completion of Part A of the Phase 1 study of SYNB8802 in Healthy Volunteers. Part B in patients with Enteric Hyperoxaluria following Roux-en-Y gastric bypass surgery has been initiated. SYNB8802 is an orally administered Synthetic Biotic medicine being developed as a potential treatment for Enteric Hyperoxaluria. Synlogic has completed dosing of five cohorts in part A, 45 total subjects. Findings include:

SYNB8802 was generally well tolerated in healthy volunteers. There were no serious or systemic adverse events. The most frequent adverse events were mild or moderate, transient, and GI-related.
Dietary Hyperoxaluria was successfully induced in Healthy Volunteers.
Subjects placed on 600 mg of daily dietary oxalate had urinary oxalate levels of 44.8 mg/24h at baseline.
Dose responsive changes in urinary oxalate levels were observed with a significant reduction in urinary oxalate relative to placebo across three dose levels.
A dose of 3e11 live cells administered three times daily with meals was selected as the dose for part B of the study.
This dose was well-tolerated and resulted in a change from baseline urinary oxalate reduction of 28.6% (90% CI: -42.4 to -11.6), compared to placebo.
At the end of dosing, the mean 24-hour urinary oxalate level was 40.1 mg for subjects treated with SYNB8802 3e11 live cells, compared to 58.1 mg for placebo subjects. Upper limit of normal urinary oxalate levels are 45 mg per 24 hours.
Full results of the study will be presented at a future medical meeting. Data from Part B in patients with Enteric Hyperoxaluria following Roux-en-Y gastric bypass surgery is expected in the second half of 2021.

The Immunomodulation Portfolio:

Advancement of SYNB1891 into combination arm dosing with PDL1 checkpoint inhibitor in an ongoing Phase 1 clinical study in patients with advanced solid tumors or lymphoma. SYNB1891 is an intratumorally administered Synthetic Biotic medicine engineered to act as a dual innate and adaptive immune activator.

SYNB1891 is currently being evaluated in a Phase 1 study that has two parts:
Part A is a monotherapy arm that has enrolled five dose cohorts to date. The maximum tolerated dose has not been reached and dose escalation continues.
Part A of the study has demonstrated target engagement and activation of the STING pathway.
Part B of the study was initiated in December 2020 and combines escalating dose levels of SYNB1891 with a fixed dose of the PD-L1 checkpoint inhibitor atezolizumab to establish a recommended Phase 2 dose for the combination regimen.
An update on the study will be shared at the American Association of Cancer Research (AACR) (Free AACR Whitepaper) meeting in April 2021.
Data from both arms will continue to be reported as appropriate over the course of 2021, with mature combination therapy data expected by the end of the year.
Corporate Update:

Synlogic expands Board of Directors. Synlogic recently appointed Michael Heffernan and Lisa Kelly-Croswell to its Board of Directors.
Mr. Heffernan is a seasoned entrepreneur and biopharmaceutical leader with over 25 years of experience building and leading development stage and commercial companies.
Ms. Kelly-Croswell is a global Human Resources executive with over 30 years of experience in assignments commonly involving rapid business growth, performance turnarounds and innovation.
Synlogic strengthens Leadership Team.
Dr. Caroline Kurtz was promoted to Chief Development Officer. Dr. Kurtz joined Synlogic in October 2016 and is responsible for program leadership and portfolio planning and progression. With over 25 years of experience in the pharmaceutical industry, Dr. Kurtz has led multiple programs through mid and late-stage clinical development.
Daniel Rosan was promoted to Senior Vice President and Head of Finance. Mr. Rosan joined Synlogic in March 2020 and has over 20 years of industry experience.
Synlogic appointed Dr. Jamie Austin to the role of Incoming Head of Regulatory Affairs. Dr. Austin has over 15 years of industry experience.
Synlogic advances strategic partnerships.
Synlogic and the MIT Voigt Lab are collaborating with the Air Force Research Laboratory (AFRL) and the Department of Defense (DoD) to engineer novel investigational medicines to address battle fatigue.
Synlogic and Ginkgo Bioworks continue to advance their long-term strategic platform collaboration that provides expanded synthetic biology capabilities to Synlogic.
Fourth Quarter 2020 Financial Results

As of December 31, 2020, Synlogic had cash, cash equivalents and short-term investments of $100.4 million.

For the three months ended December 31, 2020, Synlogic reported a consolidated net loss of $14.6 million, or $0.39 per share, compared to a consolidated net loss of $12.8 million, or $0.37 per share, for the corresponding period in 2019.

Research and development expenses were $11.4 million for the three months ended December 31, 2020 compared to $11.3 million for the corresponding period in 2019.

General and administrative expenses for the three months ended December 31, 2020 were $3.3 million compared to $3.5 million for the corresponding period in 2019.

There was no revenue for the three months ending December 31, 2020 compared to $1.2 million for the three months ended December 31, 2019. Revenue for the prior period was associated with Synlogic’s collaboration with AbbVie to develop Synthetic Biotic medicines for the treatment of Inflammatory Bowel Disease, which was terminated in May 2020.

Full Year 2020 Financial Results
For the year ended December 31, 2020, consolidated net loss was $59.2 million, or $1.65 per share, compared to a consolidated net loss of $51.4 million, or $1.70 per share, for the year ended December 31, 2019. Revenues were $0.5 million for the year ended December 31, 2020, compared to $2.2 million for the same period in 2019. Total operating expenses were $61.0 million for the year ended December 31, 2020, compared to $56.6 million for the same period in 2019.

Financial Outlook
Based upon its current operating plan, Synlogic expects to have sufficient cash to be able to fund the base operating plan into 2023.

Conference Call & Webcast Information
Synlogic will host a conference call and live webcast at 8:30 a.m. ET today, Thursday, March 25, 2021. To access the live webcast, please visit the "Event Calendar" page within the Investors and Media section of the Synlogic website. Investors may listen to the call by dialing +1 (844) 815-2882 from locations in the United States or +1 (213) 660-0926 from outside the United States. The conference ID number is 4897219. A replay will be available for 30 days on the Investors and Media section of the Synlogic website.

About PKU
Phenylketonuria (PKU) is an inherited metabolic disease that manifests at birth and is marked by an inability to break down Phe, an amino acid that is commonly found in many foods. Left untreated, high levels of Phe become toxic and can lead to serious neurological and neuropsychological problems affecting the way a person thinks, feels, and acts. Due to the seriousness of these symptoms, infants are screened at birth in many countries to ensure early diagnosis and treatment to avoid intellectual disability and other complications.

About Enteric Hyperoxaluria
Enteric Hyperoxaluria is an acquired metabolic disorder caused by increased absorption of dietary oxalate, which is present in many healthy foods, making it almost impossible to control with diet alone. Enteric Hyperoxaluria often occurs as a result of a primary insult to the bowel, such as inflammatory bowel disease, short bowel syndrome, or as a result of surgical procedures such as Roux-en-Y bariatric weight-loss surgery.

Enteric Hyperoxaluria results in dangerously high levels of urinary oxalate, which causes progressive kidney damage, kidney stone formation, and nephrocalcinosis. Enteric Hyperoxaluria has no approved treatment options.

On March 25, 2021 Istari Oncology, Inc., a clinical-stage biotechnology company, reported the publication of "Viral infection of cells within the tumor microenvironment mediates antitumor immunotherapy via selective TBK1-IRF3 signaling" in Nature Communications (Press release, Istari Oncology, MAR 25, 2021, View Source [SID1234577115]). This mechanistic study found that intratumoral PVSRIPO, via unique activation of antigen presenting cells (APCs) in the tumor microenvironment (TME), stimulates functional CD8+ T cell responses capable of mediating effective, systemic antitumor immunity.1

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Research from multiple laboratories has demonstrated the importance of APCs, especially dendritic cells, in stimulating antigen-specific immunity.2,3 When activated, these cells produce an inflammatory response marked by type-I/III IFN. The current research demonstrates that nonlethal infection of APCs by PVSRIPO triggers a distinctive pattern of robust, sustained type-I/III IFN secretion, with minimal release of unwanted proinflammatory cytokines, due to PVSRIPO’s selective effect on a specific signaling pathway. The result is effective generation of functional antitumor CD8+ T cells. The functionality of these cells was confirmed by gold-standard methods in which antitumor T cells generated in tumor-bearing mice treated with PVSRIPO could be transferred to untreated tumor-bearing mice, resulting in decreased cancer growth.

"The potential utility of a RNA virus-based immunotherapy like PVSRIPO is its natural ability to prime and activate functional cytotoxic T cell responses," said Dr. Matthias Gromeier, the senior author of the study. "PVSRIPO is genetically engineered to elicit potent, sustained innate antiviral inflammatory patterns, which yield vigorous CD8+ T cell responses in the TME, without significant toxicity. PVSRIPO’s activation of a specific pattern recognition receptor, MDA5, leads to the optimal cytokine signature — the sustained, type-I/III IFN-dominant response that is required to achieve robust anticancer immunity."

Dr. Garrett Nichols, Istari Chief Medical Officer added, "Uniquely, PVSRIPO intratumoral replication also triggers CD4-mediated immunologic recall responses made possible by prior polio vaccination, which directly engages the powerful adaptive arm of the immune system. Along with the enduring, nonlethal infection of APCs demonstrated in this report and others,4 PVSRIPO triggers the critical steps required for both a direct anticancer effect and establishment of long-term anticancer immunologic memory to help keep cancer at bay. Our upcoming LUMINOS-102 study (NCT04577807) will further evaluate the ability of PVSRIPO to generate a systemic immune response that fights cancer in both injected and noninjected tumors and suppresses cancer growth over time, expanding on the observations in the phase 1 trial in patients with unresectable, advanced, anti–PD-1 refractory melanoma.5"

"To appreciate the importance of these results, you need to consider the approach of other investigational immunotherapies," commented Matt Stober, President and CEO. "In contrast to PVSRIPO, many viral agents being studied as cancer therapies are based on pathogens that employ strategies to evade the immune system by interfering with or blocking CD8+ T cell responses — the exact responses that are required for systemic anticancer immunity."

For more information about Istari Oncology and their ongoing clinical trials and research in PVSRIPO, visit istarioncology.com.

About PVSRIPO
PVSRIPO is an investigational immunotherapy based on the live attenuated Sabin type 1 poliovirus vaccine that has been genetically modified for safety. PVSRIPO has a distinct target (the poliovirus receptor, CD155), which is widely expressed in neoplastic cells of most solid tumors. Via CD155, PVSRIPO targets tumors with two primary mechanisms: 1) direct damage to and killing of cancerous cells; and 2) engaging innate and adaptive antitumor immune responses via nonlethal infection of antigen presenting cells in the tumor, which stimulates a specific signaling pathway resulting in a sustained, robust type-I/III IFN-dominant response, with minimal release of unwanted cytokines. Its effects are potentiated by prior vaccination against poliovirus. PVSRIPO has been granted Breakthrough Therapy Designation and Orphan Status by the FDA in recurrent glioblastoma. PVSRIPO has also been granted Orphan Status by the FDA for advanced melanoma.