On May 5, 2022 BioCryst Pharmaceuticals, Inc. (Nasdaq:BCRX) reported financial results for the first quarter ended March 31, 2022, and provided a corporate update (Press release, BioCryst Pharmaceuticals, MAY 5, 2022, View Source [SID1234613611]).

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"We are now over a year into the ORLADEYO launch and are excited to see strong and continuing patient demand and steady expansion in our prescriber base among both new and existing prescribers. These trends continued in the first quarter of 2022 and reinforce our confidence that we will achieve no less than $250 million in net ORLADEYO revenue in 2022 and peak ORLADEYO sales of $1 billion," said Jon Stonehouse, president and chief executive officer of BioCryst.

"We also have made substantial progress in our investigation with BCX9930. Based on our initial findings, we believe that both dose and dosing regimen could be contributing factors to the safety signal we have observed. By the end of the third quarter, we plan to discuss our proposed approach to resume the REDEEM trials, under a revised dosing protocol, with regulators," Stonehouse added.

Program Updates and Key Milestones

ORLADEYO (berotralstat): Oral, Once-daily Treatment for Prevention of Hereditary Angioedema (HAE) Attacks

U.S. Launch

ORLADEYO net revenue in the first quarter of 2022 was $49.7 million.
Approximately 50 percent of patients currently on ORLADEYO have switched from another prophylactic therapy, and half of those patients have come from lanadelumab. These trends continued with new patients starting ORLADEYO in Q1 2022.
In the first quarter, new patient prescriptions were evenly split between repeat prescribers and new prescribers, with an approximately equal number of new prescriptions coming from the top 500 HAE treaters and the broader set of other HAE treaters.
The company has completed its latest quarterly survey of another 60 allergists who treat an average of eight HAE patients. These physicians were already using ORLADEYO on 13 percent of their patients and predicted growth to 23 percent over the next 12 months. These findings were in line with previously reported market research from August 2021.
Approximately 80 percent of HAE patients in the U.S. are insured by payors and pharmacy benefit managers that cover ORLADEYO. Despite prior authorization headwinds early in 2022, approximately 80 percent of patients on ORLADEYO were receiving paid product by the end of the first quarter, a substantial increase from approximately 66 percent of patients in the second half of 2021.
Most patients are well-controlled on ORLADEYO and remain on therapy. Once payor prior authorization is complete, 78 percent of patients switching from lanadelumab and 73 percent of patients switching from subcutaneous C1 inhibitor remain on ORLADEYO for at least six months. About 70 percent of all patients who receive reimbursed product stay on ORLADEYO for at least 12 months, compared to 60 percent of patients who remain on long-term free product.
The company expects steady quarterly ORLADEYO net revenue growth throughout the remainder of 2022, with total 2022 ORLADEYO net revenue of no less than $250 million.
"We are very pleased that strong patient demand continued to drive growth in the first quarter and overcome the traditional Q1 reimbursement headwinds. With outstanding reimbursement in place, patients continuing to enjoy an excellent experience on ORLADEYO and the expansion of both our new and existing prescriber bases, we expect steady growth throughout the remainder of 2022 as we achieve no less than $250 million in ORLADEYO net revenues for the year," said Charlie Gayer, chief commercial officer of BioCryst.

ORLADEYO: Global Updates

ORLADEYO has been launched in Denmark, France, Germany, Japan, Norway, Sweden, the United Arab Emirates and the United Kingdom. The company expects launches in additional countries throughout the year.
Complement Oral Factor D Inhibitor Program – BCX9930

On April 8, 2022, BioCryst announced that the company was voluntarily pausing enrollment in BCX9930 clinical trials while it investigated observed elevations in serum creatinine seen in some patients.

Patients in the REDEEM-1, REDEEM-2 and RENEW clinical trials randomized to BCX9930 began those trials by starting immediately at a dose of 500 mg twice-daily. Patients receiving BCX9930 in the long-term extension trial started at lower doses as part of the proof-of-concept dose escalation regimen and were ultimately moved up to 500 mg twice-daily.

Preliminary evidence from the investigation points to both the 500 mg twice-daily dosing level and the immediate start of that dose, without a period at a lower dose first, as plausible contributory factors for the observed increases in serum creatinine.

Based on the initial results of the investigation, and the safety and efficacy data observed in the BCX9930 clinical program at 400 mg twice-daily, the company plans to discuss with regulators whether clinical trials with amended protocols could resume using stepped dosing to 400 mg twice-daily. The company expects to have discussions with regulators by the end of the third quarter.

During the ongoing investigation the company has observed the following:

Three patients with PNH receiving BCX9930 in the REDEEM trials had early onset, and moderate or severe, elevations in their serum creatinine (2-4 xULN) after several weeks of dosing with 500 mg twice-daily. Two of these patients have been discontinued from therapy and one patient (who had the smallest increase in serum creatinine) continues on BCX9930 at this time.
The company estimates that one-third of subjects randomized to BCX9930 in the REDEEM studies have had early increases in serum creatinine.
The company also found a different pattern of slowly evolving, late onset, mild to moderate increases in serum creatinine in approximately 40 percent of patients in the long-term extension of the proof-of-concept trial, after those patients switched to the 500 mg twice-daily dose. This pattern was not observed during treatment with doses lower than 500 mg.
Subsequent to BioCryst voluntarily pausing trial enrollments, the U.S. Food and Drug Administration (FDA) informed the company that it has placed the clinical program for BCX9930 on a partial clinical hold. Consistent with BioCryst’s voluntary action, the company may not enroll new patients in its BCX9930 clinical trials, however patients already enrolled who are receiving clinical benefit from BCX9930 treatment, and have no other available treatment options, can continue to be dosed and remain in the trials.

"As we complete our investigation, we will continue to be comprehensive and deliberate, with a primary focus on patient safety. After consultation with regulators, we will determine the next step for the BCX9930 program," said Dr. William Sheridan, Chief Medical Officer of BioCryst.

The company does not plan to provide additional updates on the BCX9930 program until it completes additional regulatory discussions and has more clarity on the next steps for the program.

Additional Updates

On February 8, 2022, the company announced the appointment of Machelle Sanders to its board of directors.
First Quarter 2022 Financial Results

For the three months ended March 31, 2022, total revenues were $49.9 million, compared to $19.1 million in the first quarter of 2021 (+161.3 percent year-over-year (y-o-y)). The increase was primarily due to $49.7 million in ORLADEYO net revenue in the first quarter of 2022, compared to $10.9 million in ORLADEYO net revenue in the first quarter of 2021 (+356.0 percent y-o-y).

Research and development (R&D) expenses for the first quarter of 2022 increased to $65.4 million from $42.4 million in the first quarter of 2021 (+54.2 percent y-o-y), primarily due to increased investment in the development of our Factor D program, including BCX9930, as well as other research, preclinical and development costs.

Selling, general and administrative (SG&A) expenses for the first quarter of 2022 increased to $34.3 million, compared to $22.1 million in the first quarter of 2021 (+55.2 percent y-o-y). The increase was primarily due to increased investment to support the commercial launch of ORLADEYO and expanded international operations.

Interest expense was $23.8 million in the first quarter of 2022, compared to $12.9 million in the first quarter of 2021 (+84.5 percent y-o-y). The increase was due to service on the royalty financings, which were completed in November 2021.

Net loss for the first quarter of 2022 was $74.2 million, or $0.40 per share, compared to a net loss of $64.3 million, or $0.36 per share, for the first quarter of 2021.

Cash, cash equivalents, restricted cash and investments totaled $446.8 million at March 31, 2022, compared to $244.4 million at March 31, 2021. Operating cash use for the first quarter of 2022 was $71.0 million.

Financial Outlook for 2022

Based on the strength of the ORLADEYO launch, and continued steady growth from new patient demand anticipated throughout the year, the company expects full year 2022 net ORLADEYO revenue to be no less than $250 million.

The company had previously expected operating expenses for full year 2022, not including non-cash stock compensation, to be between $440 million to $480 million. Once the company completes its investigation into BCX9930 and has clarity on the next step for the program it expects to provide an updated outlook on full year 2022 operating expenses. If BCX9930 program enrollment resumes, then operating expenses are likely to be at the lower end of the previously provided range. If we discontinue the BCX9930 program, then operating expenses for the year would be lower than that.

Conference Call and Webcast

BioCryst management will host a conference call and webcast at 8:30 a.m. ET today to discuss the financial results and provide a corporate update. The live call may be accessed by dialing 877-303-8027 for domestic callers and 760-536-5165 for international callers and using conference ID # 9498023. A live webcast of the call and any slides will be available online at the investors section of the company website at www.biocryst.com. A telephone replay of the call will be available by dialing 855-859-2056 for domestic callers or 404-537-3406 for international callers and entering the conference ID # 9498023.

On May 5, 2022 Regulus Therapeutics Inc. (Nasdaq: RGLS), a biopharmaceutical company focused on the discovery and development of innovative medicines targeting microRNAs (the "Company" or "Regulus"), reported that it will report its first quarter 2022 financial results on Thursday, May 12, 2022, after the U.S. financial markets close (Press release, Regulus, MAY 5, 2022, View Source [SID1234613655]).

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In connection with the earnings release, Regulus’ management team will host a live conference call and webcast at 5:00 PM ET on Thursday, May 12, 2022, to discuss the Company’s financial results and provide a corporate update. To access the call, please dial (866) 652-5200 (domestic) or (412) 317-6060. To access the telephone replay of the call, dial (877) 344-7529 (domestic) or (412) 317-0088 and refer to conference ID 6812601. The webcast and telephone replay will be archived on the Company’s website at www.regulusrx.com following the call.

On May 5, 2022 Arvinas, Inc. (Nasdaq: ARVN), a clinical-stage biotechnology company creating a new class of drugs based on targeted protein degradation, reported financial results for the first quarter ended March 31, 2022 and provided a corporate update (Press release, Arvinas, MAY 5, 2022, View Source [SID1234613671]).

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"It has been a very productive first quarter for Arvinas, as we prepare to initiate three planned pivotal clinical studies in the second half of 2022 for our two lead programs – ARV-471 in metastatic breast cancer and bavdegalutamide in molecularly defined metastatic castration-resistant prostate cancer," said John Houston, Ph.D., chief executive officer and president at Arvinas. "We have a unique opportunity to bring these two programs into late-stage development at the same time, demonstrating the potential of our PROTAC platform to selectively and efficiently degrade and remove disease-causing proteins."

Business Highlights and Recent Developments

In February, Arvinas presented completed Phase 1 dose escalation data and interim data from the ongoing Phase 2 ARDENT expansion cohort with bavdegalutamide in metastatic castration-resistant prostate cancer (mCRPC) at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Genitourinary Cancers Symposium (ASCO GU), that showed:
A PSA50 rate (reduced prostate-specific antigen (PSA) levels greater than or equal to 50%) of 46% in patients with AR T878X/H875Y (T878X = T878A or T878S) tumor mutations (n=28)
Two durable, confirmed RECIST (Response Evaluation Criteria in Solid Tumors) partial responses (out of seven RECIST-evaluable patients with AR T878X/H875Y tumor mutations)
Bavdegalutamide had a manageable tolerability profile at the recommended Phase 2 dose (RP2D) of 420 mg oral, once daily
PSA reductions and evidence of anti-tumor activity as measured by RECIST were observed across all subgroups regardless of mutation status, including in patients with tumors not harboring AR T878X/875Y mutations
Anticipated 2022 Milestones and Expectations

ARV-471

Present data from the VERITAC Phase 2 expansion trial (200 mg and 500 mg) (2H 2022)
Present safety data from the Phase 1b combination trial with palbociclib (2H 2022)
Initiate two Phase 3 trials in patients with metastatic breast cancer (as monotherapy and in combination) (2H 2022)
Initiate a Phase 1b combination trial with cyclin dependent kinase (CDK) inhibitors or other targeted therapies (2H 2022)
Initiate a Phase 1b combination trial with everolimus (2H 2022)
Initiate a Phase 2 neoadjuvant trial in patients with early breast cancer (2H 2022)
Bavdegalutamide (ARV-110)

Discuss the potential accelerated approval path with the Food and Drug Administration (FDA) (Q2 2022)
Finalize partnership for a companion diagnostic (Q2 2022)
Initiate a pivotal trial in mCRPC for patients with AR T878/H875 tumor mutations (2H 2022)
ARV-766

Share Phase 1 dose escalation data in mCRPC (2H 2022)
Initiate Phase 2 expansion trial in mCRPC (2H 2022)
First Quarter Financial Results

Cash, Cash Equivalents, Restricted Cash and Marketable Securities Position: As of March 31, 2022, cash, cash equivalents, restricted cash and marketable securities were $1,432.9 million as compared with $1,507.1 million as of December 31, 2021. The decrease in cash, cash equivalents, restricted cash and marketable securities of $74.2 million for the first three months of 2022 was primarily related to cash used in operating activities of $60.5 million (net of $6.5 million received from two collaborators), unrealized loss on marketable securities of $14.1 million, and the purchase of lab equipment and leasehold improvements of $2.1 million, partially offset by proceeds from the exercise of stock options of $2.5 million.

Research and Development Expenses: Research and development expenses were $64.0 million for the quarter ended March 31, 2022, as compared with $34.9 million for the quarter ended March 31, 2021. The increase in research and development expenses of $29.1 million for the quarter was primarily due to an increase in our continued investment in our platform and exploratory programs of $11.0 million, as well as an increase in expenses related to our AR program (which includes bavdegalutamide and ARV-766) of $8.9 million and our ER program of $9.2 million, which is net of the cost sharing of ARV-471 under the global Pfizer collaboration agreement to develop and commercialize ARV-471 that was initiated in July 2021 (ARV-471 Collaboration Agreement).

General and Administrative Expenses: General and administrative expenses were $20.2 million for the quarter ended March 31, 2022, as compared with $12.3 million for the quarter ended March 31, 2021. The increase of $7.9 million was primarily due to an increase in personnel and facility related costs of $5.5 million and insurance and professional fees of $2.4 million.

Revenues: Revenues were $24.2 million for the quarter ended March 31, 2022, as compared with $5.5 million for the quarter ended March 31, 2021. Revenue is related to the ARV-471 Collaboration Agreement, the license and rights to technology fees and research and development activities related to the collaboration and license agreement with Bayer that was initiated in July 2019, the collaboration and license agreement with Pfizer that was initiated in January 2018, and the amended and restated option, license and collaboration agreement with Genentech that was initiated in November 2017. The increase in revenues of $18.7 million was due to revenue from the ARV-471 Collaboration Agreement.

Income Tax Expense: Income tax expense was $4.5 million for the quarter ended March 31, 2022, as compared with zero for the quarter ended March 31, 2021, due to taxable income projected for fiscal year 2022 primarily related to revenue recognized in 2022 for tax purposes from the ARV-471 Collaboration Agreement.

Net Loss: Net loss was $63.4 million for the quarter ended March 31, 2022, as compared with $41.0 million for the quarter ended March 31, 2021. The increase in net loss for the quarter was primarily due to increased research and development expenses, general and administrative expenses, and income tax expense, partially offset by increased revenue.

About bavdegalutamide (ARV-110)
Bavdegalutamide (ARV-110) is an investigational orally bioavailable PROTAC protein degrader designed to selectively target and degrade the androgen receptor (AR). Bavdegalutamide is being developed as a potential treatment for men with metastatic castration-resistant prostate cancer.

Bavdegalutamide has demonstrated activity in preclinical models of AR mutation or overexpression, both common mechanisms of resistance to currently available AR-targeted therapies.

About ARV-471
ARV-471 is an investigational orally bioavailable PROTAC protein degrader designed to specifically target and degrade the estrogen receptor (ER) for the treatment of patients with locally advanced or metastatic ER+/HER2- breast cancer.

In preclinical studies, ARV-471 demonstrated near-complete ER degradation in tumor cells, induced robust tumor shrinkage when dosed as a single agent in multiple ER-driven xenograft models, and showed superior anti-tumor activity when compared to a standard of care agent, fulvestrant, both as a single agent and in combination with a CDK4/6 inhibitor. In July 2021, Arvinas announced a global collaboration with Pfizer for the co-development and co-commercialization of ARV-471; Arvinas and Pfizer will equally share worldwide development costs, commercialization expenses, and profits.

About ARV-766
ARV-766 is an investigational orally bioavailable PROTAC protein degrader designed to selectively target and degrade AR. In preclinical studies, ARV-766 degraded all resistance-driving point mutations of AR, including L702H, a mutation associated with treatment with abiraterone and other AR-pathway therapies.

ARV-766 is being developed as a potential treatment for men with metastatic castration-resistant prostate cancer, and ARV-766 may also have applicability in other AR-driven diseases both in and outside oncology. ARV-766 has demonstrated activity in preclinical models of resistance to currently available AR-targeted therapies.

On May 5, 2022 Genprex, Inc. ("Genprex" or the "Company") (NASDAQ: GNPX), a clinical-stage gene therapy company focused on developing life-changing therapies for patients with cancer and diabetes, reported that it has issued a shareholder letter and corporate update outlining the Company’s recent progress in its clinical development programs and key milestones and achievements for 2022 and beyond (Press release, Genprex, MAY 5, 2022, View Source [SID1234613687]).

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"We have had a strong start to this year, achieving many key milestones for our Company," said Rodney Varner, President and Chief Executive Officer of Genprex. "We announced our second Fast Track Designation for REQORSA Immunogene Therapy, we commenced patient treatment in our Phase 1/2 Acclaim-1 clinical trial for non-small cell lung cancer (NSCLC), we opened our Phase 1/2 Acclaim-2 clinical trial for NSCLC and commenced patient treatment in that trial (having treated the first patient in April 2022), and we expanded our clinical development pipeline to include small cell lung cancer (SCLC). I am enthusiastic about our future as we continue to advance our leading edge gene therapy programs with the goal of extending hope and life to patients with serious disease and unmet need."

To read the letter in its entirety, a digital copy of the Company’s Shareholder Letter can be found on the Company’s website here.

On May 5, 2022 SQZ Biotechnologies (NYSE: SQZ) reported that the company will present data from the first non-clinical studies of its point-of-care (POC) manufacturing system at the 2022 American Society for Gene and Cell Therapy (ASGCT) (Free ASGCT Whitepaper) Annual Meeting on May 18 (Press release, SQZ Biotech, MAY 5, 2022, View Source [SID1234613703]). The data will demonstrate an ability to produce SQZ cell therapy candidates with comparable or improved performance relative to conventional clean room manufacturing processes. In addition, SQZ announced a collaboration with STEMCELL Technologies to co-develop and commercialize a research-use-only (RUO) microfluidic intracellular delivery system. The new RUO system will be based on SQZ’s Cell Squeeze technology and will offer the life sciences community access to a unique cell engineering capability to advance preclinical research. These activities support SQZ’s mission to unlock the full potential of cell therapies for multiple therapeutic areas.

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"SQZ’s vision is to improve patient care by creating transformative cell therapies that can be broadly accessible around the world through rapid, cost-efficient manufacturing," said Armon Sharei, Ph.D., CEO and Founder at SQZ Biotechnologies. "We are advancing these important goals through the development of our POC manufacturing system, which has the potential to substantially improve the accessibility and economic feasibility of cell therapies. Through our collaboration with STEMCELL, we intend to broaden technology access for research use and hope to facilitate advancement of the cell therapy field by the life sciences community."

"This is an exciting collaboration that combines STEMCELL’s life sciences research and product development capabilities with SQZ’s cell engineering expertise," said Allen Eaves, M.D., Ph.D., President and CEO of STEMCELL Technologies. "The development of this RUO system, which will be well complemented by our various cell isolation and culture product portfolios, will provide the research community with a significant opportunity for their cell engineering investigations. By adapting the proven Cell Squeeze technology, with its ability to deliver multiple biological cargoes to a range of cell types, we anticipate the RUO system will offer enhanced flexibility to the scientific community. We look forward to our continued collaboration with SQZ and the development of this system."

SQZ’s Cell Squeeze technology has enabled the development of three oncology therapeutic candidates in active Phase 1/2 clinical trials. In addition to these programs, the company intends to file its first IND using the POC system for a SQZ TAC clinical candidate against celiac disease in the first half of 2023. The Cell Squeeze technology has also led to a number of preclinical developments in the areas of infectious disease and cell regeneration.

SQZ’s automated POC manufacturing system in development integrates, among other things, cell isolation, cell washing, intracellular delivery, and product filling. The system is designed to process patient material within a closed, single-use sterile disposable kit. The prototype system offers the potential to be operated outside of a clean room—which could ultimately allow decentralized cell therapy manufacturing by SQZ POC systems in a variety of care settings. SQZ will present data from the initial non-clinical studies of the POC system at ASGCT (Free ASGCT Whitepaper).

STEMCELL Technologies will present data from the first functional study findings for the RUO system at the ASGCT (Free ASGCT Whitepaper) Annual Meeting. The data will demonstrate an ability to efficiently deliver cargoes to primary immune cell types. SQZ will also present new cell engineering data in hematopoietic stem cells using mRNA and CRISPR/Cas9 at the meeting.

ASGCT PRESENTATION TITLES AND TIMING

SQZ Point-of-Care Manufacturing Presentation
Title: A Decentralized and Integrated Manufacturing System for the Rapid and Cost-Effective Production of Cell Therapy Drug Products
SQZ Presenter: Maisam Dadgar
Session Title: Cell Therapy Product Engineering, Development or Manufacturing
Abstract Number: 1171
Date & Time: Wednesday, May 18, 2022, from 5:30-6:30 PM

STEMCELL TECHNOLOGIES Immune Cell Engineering Research Poster Presentation
Title: A New Benchtop System for Simple and Versatile Introduction of Macromolecules into Human Lymphocytes by Microfluidic Squeezing
STEMCELL Presenter: Eric Ouellet, Ph.D.
Session Title: Synthetic/Molecular Conjugates and Physical Methods for Delivery II
Abstract Number: 997
Date & Time: Wednesday, May 18, 2022, from 5:30-6:30 PM

SQZ Hematopoietic Stem Cell Research
Title: Rapid, Gentle, and Scalable Engineering of Hematopoietic Stem Cells Using Vector-Free Microfluidic Cell Squeeze Technology
SQZ Presenter: Murillo Silva, Ph.D.
Session Title: Cell Therapy Product Engineering, Development or Manufacturing
Abstract Number: 1176
Date & Time: Wednesday, May 18, 2022, from 5:30-6:30 PM