On May 31, 2022 ChemoCentryx, Inc., (Nasdaq: CCXI), reported upcoming abstract presentations at three key medical conferences taking place in June, which highlight TAVNEOS (avacopan), an orally administered selective complement 5a receptor (C5aR) inhibitor, and its role in ANCA-associated vasculitis and potential application in C3 glomerulopathy, as well as the immuno-oncology potential of CCX559, an orally administered small molecule PD-L1 inhibitor (Press release, ChemoCentryx, MAY 31, 2022, View Source [SID1234615357]).

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European Alliance of Associations for Rheumatology (EULAR), June 1-4, Copenhagen

Effect of Avacopan on Relapse Rates and Relapse-Free Time in Patients with ANCA-Associated Vasculitis: Results of the Phase 3 ADVOCATE Study

Oral Presentation: OP0180
Time: June 2, 2022, at 10:35 – 10:45 AM CEST
Session: Vessels glowing in the dark
Location: Congress Hall A2
Differences Between Avacopan & Prednisone Treatment of ANCA-Associated Vasculitis at Different Thresholds of Glucocorticoid Toxicity

Poster: POS0833
Available: June 1, 2022, 08:00 AM CEST
Poster View 5: June 1, 2022, 01:20 – 01:28 PM CEST
Relapse Rates in Newly Diagnosed and Established Patients with Anti-Neutrophil Cytoplasmic Autoantibody (ANCA)-Associated Vasculitis

Poster: POS0835
Available: June 1, 2022, 08:00 AM CEST
Poster View 5: June 1, 2022, 01:36 – 01:44 PM CEST
American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper), June 3-7, Chicago

Results From an Ongoing Phase 1 Dose-Escalation Study of CCX559, an Orally Administered Small Molecule PD-L1 Inhibitor, in Patients With Advanced Solid Tumors

Poster: 248 (Abstract: 2593)
Time: Sunday, June 5 at 8:00 – 11:00 AM CDT
Session: Developmental Therapeutics – Immunotherapy
European Society for Pediatric Nephrology (ESPN), June 22-25, Ljubljana, Slovenia

Safety and Efficacy of Avacopan (CCX168) in a Pediatric Patient with C3 Glomerulopathy

E-Poster Available: June 22, 2022
INDICATION

TAVNEOS (avacopan) is indicated as an adjunctive treatment of adult patients with severe active anti-neutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis (granulomatosis with polyangiitis [GPA] and microscopic polyangiitis [MPA]) in combination with standard therapy including glucocorticoids. TAVNEOS does not eliminate glucocorticoid use.

IMPORTANT SAFETY INFORMATION

CONTRAINDICATIONS

Serious hypersensitivity to avacopan or to any of the excipients

WARNINGS AND PRECAUTIONS

Hepatotoxicity: Serious cases of hepatic injury have been observed in patients taking TAVNEOS, including life-threatening events. Obtain liver test panel before initiating TAVNEOS, every 4 weeks after start of therapy for six months and as clinically indicated thereafter. Monitor patients closely for hepatic adverse reactions and consider pausing or discontinuing treatment as clinically indicated (refer to section 5.1 of the Prescribing Information). TAVNEOS is not recommended for patients with active, untreated and/or uncontrolled chronic liver disease (e.g., chronic active hepatitis B, untreated hepatitis C, uncontrolled autoimmune hepatitis) and cirrhosis. Consider the risk and benefit before administering this drug to a patient with liver disease.

Serious Hypersensitivity Reactions: Cases of angioedema occurred in a clinical trial, including one serious event requiring hospitalization. Discontinue immediately if angioedema occurs and manage accordingly. TAVNEOS must not be re-administered unless another cause has been established.

Hepatitis B Virus (HBV) Reactivation: Hepatitis B reactivation, including life threatening hepatitis B, was observed in the clinical program. Screen patients for HBV. For patients with evidence of prior infection, consult with physicians with expertise in HBV and monitor during TAVNEOS therapy and for six months following. If patients develop HBV reactivation, immediately discontinue TAVNEOS and concomitant therapies associated with HBV reactivation and consult with experts before resuming.

Serious Infections: Serious infections, including fatal infections, have been reported in patients receiving TAVNEOS. The most common serious infections reported in TAVNEOS group were pneumonia and urinary tract infections. Avoid use of TAVNEOS in patients with active, serious infection, including localized infections. Consider the risks and benefits before initiating TAVNEOS in patients with chronic infection, at increased risk of infection or who have been to places where certain infections are common.

ADVERSE REACTIONS

The most common adverse reactions (≥5% of patients and higher in the TAVNEOS group vs. prednisone group) were: nausea, headache, hypertension, diarrhea, vomiting, rash, fatigue, upper abdominal pain, dizziness, blood creatinine increased and paresthesia.

DRUG INTERACTIONS

Avoid coadministration of TAVNEOS with strong and moderate CYP3A4 enzyme inducers. Reduce TAVNEOS dose when co-administered with strong CYP3A4 enzyme inhibitors to 30 mg once daily. Monitor for adverse reactions and consider dose reduction of certain sensitive CYP3A4 substrates.

Please see Full Prescribing Information and Medication Guide for TAVNEOS.

About TAVNEOS (avacopan)

TAVNEOS (avacopan), approved by the FDA as an adjunctive treatment of ANCA-associated vasculitis, is a first-in-class, orally administered small molecule that employs a novel, highly targeted mode of action in complement-driven autoimmune and inflammatory diseases. While the precise mechanism in ANCA vasculitis has not been definitively established, TAVNEOS, by blocking the complement 5a receptor (C5aR) for the pro-inflammatory complement system fragment known as C5a on destructive inflammatory cells such as blood neutrophils, is presumed to arrest the ability of those cells to do damage in response to C5a activation, which is known to be the driver of ANCA vasculitis. TAVNEOS’s selective inhibition of only the C5aR is believed to leave the beneficial C5a pathway through the C5L2 receptor functioning normally.

ChemoCentryx is also developing TAVNEOS for the treatment of patients with C3 glomerulopathy (C3G), severe hidradenitis suppurativa (HS) and Lupus Nephritis (LN). The US Food and Drug Administration granted TAVNEOS orphan drug designation for ANCA-associated vasculitis and C3G. The European Commission has granted orphan medicinal product designation for TAVNEOS for the treatment of two forms of ANCA-associated vasculitis: microscopic polyangiitis and granulomatosis with polyangiitis (formerly known as Wegener’s granulomatosis), as well as for C3G. TAVNEOS has not been approved for indications discussed as in development, and the safety and efficacy of those uses has not been established.

About ANCA-Associated Vasculitis

ANCA-associated vasculitis is a systemic disease in which over-activation of the complement pathway further activates neutrophils, leading to inflammation and destruction of small blood vessels. This results in organ damage and failure, with the kidney as the major target, and is fatal if not treated. Currently, treatment for ANCA-associated vasculitis consists of courses of non-specific immuno-suppressants (cyclophosphamide or rituximab), combined with the administration of daily glucocorticoids (steroids) for prolonged periods of time, which can be associated with significant clinical risk including death from infection.

On May 31, 2022 Sermonix Pharmaceuticals Inc., a privately held biopharmaceutical company developing innovative therapeutics to specifically treat ESR1-mutated metastatic breast and gynecological cancers, reported two abstracts accepted for presentation at the 2022 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting, which is being held June 3-7 at McCormick Place in Chicago, and online (Press release, Sermonix Pharmaceuticals, MAY 31, 2022, View Source [SID1234615328]).

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"We are very pleased to be able to present compelling data from our ELAINE-2 study at this year’s ASCO (Free ASCO Whitepaper) meeting," stated Dr. David Portman, founder and chief executive officer of Sermonix. "It has been well established that the development of ESR1 mutations is strongly associated with increasing resistance to aromatase inhibitor (AI) therapies, disease progression and poor long-term outcomes. Our ELAINE-2 study is evaluating investigational lasofoxifene in combination with the CDK4/6 inhibitor abemaciclib for the treatment of metastatic breast cancer with an ESR1 mutation. Lasofoxifene plus abemaciclib met the primary and secondary study endpoints in these women who had progressed on previous CDK4/6i therapies. We are encouraged by the results to date from this study and are excited to move forward with our clinical development program for lasofoxifene. ELAINE-2 is the first study to show positive efficacy results with a selective estrogen receptor modulator (SERM) and CDK4/6 in this challenging post-CDK4/6 treated population.

"Based on these data, we believe lasofoxifene, as the only SERM currently being developed exclusively to treat breast cancers with ESR1 mutations, has the potential, if approved, to play a critical role in the targeted precision medicine treatment of advanced ER+ breast cancer. Because of our belief that lasofoxifene can be an endocrine backbone of choice, we are planning to study it in combination with other therapies in mBC patients who have an ESR1 mutation.

"In parallel, our ELAINE-1 study, which is assessing lasofoxifene as monotherapy compared to fulvestrant for the treatment of metastatic breast cancer with an ESR1 mutation post-CDK4/6i therapy, is fully enrolled, and we will be presenting data in late Q3 of this year," Dr. Portman concluded.

Details of the presentations are as follows:

Title: Open-label, Phase 2, Multicenter Study of Lasofoxifene (LAS) Combined with Abemaciclib (Abema) for Treating Pre- and Post-Menopausal Women with Locally Advanced or Metastatic ER+/HER2− Breast Cancer and an ESR1 Mutation after Progression on Prior Therapies

Abstract number: 1022

Session type: Poster Discussion

Session: Breast Cancer – Metastatic

Date: Monday, June 6, 2022

Time: 9 a.m.-12 p.m. EDT

From the summary, resistance to endocrine therapy can develop when treating estrogen receptor positive (ER+), metastatic breast cancer (mBC). Treatment with aromatase inhibitors can lead to acquired mutations in the estrogen receptor 1 (ESR1), which can constitutively activate the ER, leading to endocrine resistance, metastases and worse disease prognosis. Treatment options for mBC patients with an ESR1 mutation are limited. Further, retrospective data suggest that patients could derive clinical benefit from Abema after progression on prior cyclin-dependent kinase 4/6 inhibitor (CDK4/6i).1

ELAINE-2 is an open-label, phase 2, multicenter trial evaluating the safety and efficacy of LAS combined with the CDK4/6i, Abema. Study participants were pre- and postmenopausal women with ER+/HER2- mBC with acquired ESR1 mutation (identified by ctDNA testing), whose disease had progressed on one or two lines of hormonal therapy for metastatic disease with or without a CDK4/6i (including Abema). Abema (Verzenio) was provided through a drug supply collaboration with Eli Lilly and Co. Treatment continued until evidence of disease progression, death, unacceptable toxicity or withdrawal from the study. The primary endpoint was safety, and secondary endpoints were progression free survival (PFS), objective response rate (ORR) and clinical benefit rate (CBR).

Results: 29 patients were enrolled, and most had progressed with at least two previous hormonal treatments (80%). All except one patient received a prior CDK4/6i and 72% had received prior fulvestrant; 48% had chemotherapy in the metastatic setting. To date, 11 patients have progressed and 14 continue treatment. Median PFS was 13.9 months, ORR was 33.3% and CBR was 62.1% at the time of analysis.

Title: Operational Metrics for the ELAINE II Study Combining a Traditional Approach with a Just-in-Time Model2

Abstract number: 1504

Session type: Oral Abstract

Session: Care Delivery and Regulatory Policy

Date: Monday, June 6, 2022

Time: 4 -7 p.m. EDT

Trial recruitment that requires specific actionable mutations based on next-generation sequencing (NGS) is challenging. Barriers can include competing studies, physician study awareness, site proximity, mutation incidence, among other concerns.

This study opened clinical sites using two methods during the COVID-19 pandemic. The "Traditional" approach included site selection, IRB and contract approval, and trial activation prior to a patient being identified for enrollment. The second approach used the Tempus "TIME" Trials network that would only open a site after identifying a patient with a mutation of interest and eligibility for the trial.

A total of 16 sites (6 Traditional and 10 TIME) participated. All Traditional sites, and none of the TIME sites, were affiliated with major academic institutions. Duration for full CTA execution for Traditional sites averaged 200.5 days (range 142 to 257) and for TIME sites averaged 7.6 days (range 2 to 14). IRB approval time average for Traditional sites was 27.5 days (range 12 to 71) and TIME sites was 3.0 days (range 1 to 12 days). Days from site selection to activation letter for Traditional sites was on average 250.0 days (range 187 to 281) and for TIME sites was 131.6 days (range 22 to 248). Time from study activation to first consent was 33.3 days (range 18 to 58) for Traditional sites and 8.8 days (range 1 to 35) for TIME sites. The first patient on-study was at a TIME site 115 days prior to a Traditional site and the first 7 patients enrolled were at TIME sites. Traditional sites consented 23 and enrolled 16 patients while the TIME sites consented 16 and enrolled 13. The trial enrolled all 29 patients in 8 months with the anticipated enrollment duration being 12 to 18 months.

1 Wander SA et al. J Natl Compr Canc Netw, doi: 10.6004/jnccn.2020.7662. Published online 3/24/22

Conclusion: Although the Traditional and TIME programs had different operational models, they both contributed a significant number of patients and reduced the projected enrollment timeline. TIME sites enrolled the initial patients. These results demonstrate that the "Just-in-Time model," in conjunction with a Traditional model, can reduce projected overall time to enrollment in biomarker-driven studies.

2 Abstract submitted by, and will be presented by, Tempus, a leader in artificial intelligence and precision medicine.

About Lasofoxifene

Lasofoxifene is an investigational, nonsteroidal selective estrogen receptor modulator (SERM), which Sermonix licensed globally from Ligand Pharmaceuticals Inc. (NASDAQ: LGND) and has been studied in previous comprehensive Phase 1-3 non-oncology clinical trials in more than 15,000 postmenopausal women worldwide. Lasofoxifene’s bioavailability and activity in mutations of the estrogen receptor could potentially hold promise for patients who have acquired endocrine resistance due to ESR1 mutations, a common finding in the metastatic setting and an area of high unmet medical need. Lasofoxifene’s novel activity in ESR1 mutations was discovered at Duke University and Sermonix has exclusive rights to develop and commercialize the product in this area. Lasofoxifene, a potent, oral SERM could, if approved, play a critical role in the targeted precision medicine treatment of advanced ER+ breast cancer.

On May 31, 2022 Concert Pharmaceuticals, Inc. (NASDAQ: CNCE) reported that it intends to offer and sell 10,000,000 shares of its common stock in an underwritten registered public offering (Press release, Concert Pharmaceuticals, MAY 31, 2022, View Source [SID1234615306]). All of the shares in the offering are to be sold by Concert. The offering is subject to market and other conditions, and there can be no assurance as to whether or when the offering may be completed, or as to the actual size or terms of the offering.

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Jefferies and Truist Securities are acting as joint book-running managers for the proposed offering. Concert intends to grant the underwriters a 30-day option to purchase up to an additional 1,500,000 shares of common stock sold in the offering on the same terms and conditions.

The offering is being made only by means of a written prospectus supplement and prospectus forming part of a shelf registration statement previously filed with the Securities and Exchange Commission (SEC) and declared effective on November 16, 2020.

A preliminary prospectus supplement and accompanying prospectus relating to the offering will be filed with the SEC. Copies of the preliminary prospectus supplement and accompanying prospectus may be obtained, when available, at the SEC’s website at www.sec.gov, or by request at Jefferies LLC, Attention: Equity Syndicate Prospectus Department, 520 Madison Avenue, New York, New York 10022, by telephone at (877) 821-7388, or by email at [email protected] or Truist Securities, Inc., Attention: Prospectus Department, 3333 Peachtree Road NE, 9th floor, Atlanta, Georgia 30326, by telephone at (800) 685-4786, email: [email protected].

This press release shall not constitute an offer to sell or the solicitation of an offer to buy, nor shall there be any sale of, these securities in any state or other jurisdiction in which such offer, solicitation or sale would be unlawful prior to registration or qualification under the securities laws of any such state or other jurisdiction.

On May 31, 2022 Priothera, a late-clinical stage biotechnology company pioneering the development of its S1P receptor modulator compound, mocravimod, reported that the U.S. Food and Drug Administration (FDA) has granted Fast Track designation (FTD) for mocravimod in combination with allogeneic Hematopoietic Stem Cell Transplant (HSCT) for post remission therapy of Acute Myeloid Leukemia (AML) patients (Press release, Priothera, MAY 31, 2022, View Source [SID1234615302]). FDA’s Fast Track designation is designed to facilitate the development and expedite the review of new drugs that are intended to treat serious or life-threatening diseases and that demonstrate the potential to address unmet medical needs.

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Priothera is working to initiate the MO-TRANS global Phase 2b/3 study in Europe, US and Japan, to assess the efficacy and safety of mocravimod as an adjunctive and maintenance therapy in adult AML patients undergoing allogeneic HSCT. The MO-TRANS study is expected to start in the second half of 2022 and preliminary data from this study are expected by the end of 2024.

Karen Von Graevenitz, Head of Regulatory Affairs at Priothera, commented: "The Fast Track designation grant for mocravimod in combination with allogeneic HSCT is an important milestone and underlines the significant unmet need in AML patients undergoing HSCT, a serious disease where currently no available therapy exists. The designation means mocravimod will be eligible for expedited review and we will work closely with the US FDA to advance the global Phase 2/3 trial which is due to start in the second half of 2022."

Florent Gros, Co-Founder and CEO of Priothera, added: "Following being granted orphan drug designations for mocravimod in the US and Europe, we are pleased to have been granted Fast Track designation for this highly promising compound. This important regulatory milestone moves us a step closer to bringing mocravimod to patients with AML and other hematologic malignancies."

About mocravimod

Mocravimod (also known as KRP203), is a synthetic, sphingosine 1-phosphate receptor (S1PR) modulator. This novel investigational drug has been assessed in Phase 1 and Phase 2 trials for safety and tolerability, as well as for efficacy in several autoimmune indications. Promising data from a Phase 1b/2a clinical study in patients with hematological malignancies led Priothera to further develop mocravimod for the treatment of blood cancers.

Mocravimod will be investigated as an adjunctive and maintenance treatment in a Phase 2b/3 study as a potential treatment for patients with Acute Myeloid Leukemia (AML) receiving allogeneic hematopoietic stem cell transplantation (HSCT). Allogeneic HSCT is the only potentially curative approach for AML patients, but current treatments have unacceptably high mortality and morbidity rates.

Priothera leverages S1PR modulator’s unique mode of action to maintain anti-leukemia activity – graft-versus leukemia (GVL) while reducing tissue damage resulting from graft-versus-host disease (GVHD), a consequence of allogeneic HSCT. This novel treatment approach – mocravimod being the only S1PR modulator treating blood cancers – tackles a high unmet medical need and intends to add quality life to patients.

On May 31, 2022 Biond Biologics Ltd., a private, clinical-stage biopharmaceutical company developing novel immunotherapies for cancer and a platform enabling the intracellular delivery of biologics, reported that the company will be presenting a joint poster with Sanofi at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) 2022 Annual Meeting taking place in Chicago, Illinois, June 3-7, 2022 (Press release, Biond Biologics, MAY 31, 2022, View Source [SID1234615301]). The poster presents pre-clinical translational data including potential patient enrichment biomarkers for SAR444881 (BND-22).

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The poster will be presented at:

Developmental Therapeutics—Immunotherapy

Date and Time: 06/05/2022, 8:00 AM – 11:00 AM

Abstract Title: Evaluation of pharmacodynamic and patient enrichment biomarkers for SAR444881, a first-in-class anti-ILT2 monoclonal antibody for cancer immunotherapy.

Abstract ID: 2571

About SAR444881 (BND-22),

Leukocyte Ig-like receptor B1 (LILRB1), also known as immunoglobulin-like transcript 2 (ILT2), is an inhibitory receptor expressed on various immune cells. ILT2 was shown to bind to classical and nonclassical MHC class I molecules and with the highest affinity to HLA-G. Inhibition of ILT2 signaling axis results in impairment of immune cell proliferation, differentiation, phagocytosis, cytotoxicity and cytokine secretion and may therefor serve as a novel target for anti-cancer immunotherapy. SAR444881 (BND-22) is a novel humanized IgG4 monoclonal antagonist antibody that selectively binds to ILT2, blocking its interaction with MHC I molecules, thus preventing the inhibition of ILT2 signaling.

"We previously demonstrated that SAR444881 has robust macrophage and lymphocyte-driven anti-tumor activity in in vitro and in vivo models. The poster presents a joint effort of Biond and Sanofi to explore the pharmacodynamic effect of ILT2 antagonism as well as to inform on combinatorial and patient enrichment strategies for SAR444881 clinical development", said Ilana Mandel, Ph.D., VP R&D at Biond Biologics.