On February 23, 2022 Plexium, Inc. (Plexium), a leading next-generation targeted protein degradation (TPD) company, reported the completion of an oversubscribed $102M financing, led by BVF Partners, L.P. and TCG X, with participation from new investors Softbank Vision Fund 2, RA Capital Management, Surveyor Capital (a Citadel company), and Pappas Capital (Press release, Plexium, FEB 23, 2022, View Source [SID1234608877]). Existing investors The Column Group, DCVC Bio, Pivotal bioVenture Partners, Lux Capital, M Ventures, CRV and Neotribe Ventures also participated in the round. In connection with the financing, Cariad Chester, partner at TCG X, has joined the Plexium Board of Directors.

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"We are proud of Plexium’s significant progress toward becoming the premier targeted protein degradation company. From attracting the highest quality investors in our latest financing announced today to establishing a validating partnership with Amgen for oncology, we continue to enhance our best-in-class platform and expand our pipeline to improve patients’ lives," said Plexium President & CEO Percival Barretto-Ko. "Plexium is well positioned to accelerate our programs toward the clinic and broaden our capabilities with a comprehensive and agnostic approach across multiple TPD modalities to address the vast undrugged landscape of opportunity that remains."

The proceeds from the financing will enable Plexium to accelerate its pipeline programs toward the clinic, including a molecular glue that selectively degrades the IKZF2 transcription factor, selective degraders of CDK2 and SMARCA2, and other undisclosed high value targets. In addition, the financing will support the advancement of Plexium’s TPD platform, powered by a proprietary high-throughput cell-based screening technology, to discover novel therapies across multiple therapeutic areas including oncology and other diseases.

Cariad Chester, partner at TCG X, added, "The foundational screening technology at Plexium is uniquely capable of interrogating molecular glues and degraders in a cellular context. With an incredible team and a compelling discovery and development platform, Plexium has quickly emerged as a leader in the field of targeted protein degradation and is well-positioned to realize the potential of this transformational modality to impact patients. We are proud to co-lead this financing and look forward to supporting Plexium through its next phase of growth."

With the close of this financing, Plexium is well-capitalized with almost $200 million, including committed partnership research and development funding, to advance its pipeline and expand the capabilities of its TPD platform.

On February 23, 2022 Ensysce Biosciences, Inc. ("Ensysce" or the "Company") (NASDAQ: ENSC, OTC: ENSCW), a clinical-stage biotech company applying transformative chemistry to improve prescription drug safety and performance with a focus on reducing abuse and overdose while providing relief for those with severe pain, reported management’s participation in the 34th Annual Roth Conference being held March 13-15, 2022 at the Ritz Carlton, Laguna Niguel in Dana Point, California (Press release, Ensysce Biosciences, FEB 23, 2022, View Source [SID1234608876]).

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The Company’s Chief Executive Officer Lynn Kirkpatrick, PhD and Chief Financial Officer Dave Humphrey will be available for one-on-one and small group meetings with investors. To schedule a meeting with Ensysce management, please contact your conference representative or you may also email your request to [email protected].

The Company’s two novel proprietary platforms to develop safer prescription drugs, especially with overdose protection of MPAR, are significant considering the release of the latest data from the US Centers for Disease Control and Prevention with drug overdose deaths reaching another record high. The Company’s focus on developing the "next generation opioids" with overdose protection is aimed at providing safer alternatives for those suffering with severe pain, to reduce abuse and ultimately to save lives.

On February 23, 2022 Clovis Oncology, Inc. (NASDAQ:CLVS) reported financial results for the quarter ended December 31, 2021, and provided an update on the Company’s clinical development programs and regulatory and commercial outlook (Press release, Clovis Oncology, FEB 23, 2022, View Source [SID1234608875]).

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"We have been looking forward to 2022 for a long time, which we anticipate will be the most significant year for clinical data read-outs in the Company’s history," said Patrick J. Mahaffy, President and CEO of Clovis Oncology. "Despite the ongoing impact of COVID-19 on ovarian cancer diagnoses and treatments, and consequently on Rubraca revenues in 2021, our commitment to Phase 3 trials has potentially set the stage for significant label expansion, and therefore sales growth, in both the US and Europe. For Rubraca, we anticipate three Phase 3 read-outs during the year: ATHENA-MONO as monotherapy in the first-line ovarian cancer maintenance treatment setting now anticipated during Q2 based on a slower than expected event count, TRITON3 in the second-line prostate cancer treatment setting for selected patients during Q2, and ATHENA-COMBO in combination with Opdivo in the first-line ovarian cancer maintenance treatment setting in the fourth quarter of 2022. In addition, for FAP-2286, we continue to enroll the Phase 1 portion of LuMIERE and believe we are maintaining our lead in the clinical development of an FAP-targeted radionuclide therapeutic candidate. We and our investigators are extremely enthusiastic about this program and look forward to both presenting data at nuclear medicine meetings during 2022 and initiating the Phase 2 portion of the LuMIERE study later this year."

Fourth Quarter and Year-End 2021 Financial Results

Clovis reported global net product revenues for Rubraca of $36.0 million for Q4 2021, which included US product revenues of $27.6 million and ex-US product revenues of $8.4 million, respectively. This represents a sequential 5% decrease from Q3 2021 and a 17% decrease year-over-year, compared to Q4 2020 net product revenues of $43.3 million, which included US net product revenues of $36.4 million and ex-US net product revenues of $6.9 million. The decrease in revenues for the quarter and year was primarily due to fewer ovarian cancer diagnoses and fewer patients treated in the US related to the ongoing impact of COVID-19.

Rubraca global net product revenues for 2021 were $148.8 million, which included $115.7 million in the US and $33.1 million in ex-US product revenues, respectively. This represents a 10% percent decrease compared to 2020 net product revenues of $164.5 million, which included $146.3 million in the US and ex-US net product revenues of $18.2 million.

Research and development expenses totaled $41.8 million for Q4 2021 and $186.6 million for FY 2021, down 26% and 28%, respectively, compared to $56.7 million and $257.7 million for the comparable periods in 2020. Research and development expenses decreased for the quarter and year compared to the same periods in the prior year due primarily to lower spending on Rubraca clinical trials.

Selling, general and administrative expenses totaled $33.3 million for Q4 2021 and $128.4 million for FY 2021, down 18% and 22%, respectively, compared to $40.8 million and $163.9 million for the comparable periods in 2020. Selling, general and administrative expenses decreased during the quarter and year compared to the same periods in the prior year with savings due to the COVID-19 situation globally and overall cost reduction efforts.

Clovis reported a net loss for Q4 2021 of $64.4 million, or ($0.50) per share, and a net loss of $264.5 million, or ($2.29) per share, for FY 2021. Net loss for Q4 2020 was $99.0 million, or ($1.02) per share, and $369.2 million, or a net loss of ($4.38) per share, for FY 2020. Net loss for Q4 and FY 2021 included share-based compensation expense of $7.1 million and $25.5 million, compared to $12.0 million and $50.8 million for the comparable periods of 2020.

Clovis had $143.4 million in cash and cash equivalents as of December 31, 2021. During Q4 2021, the Company raised $3.0 million in net proceeds, and in Q1 2022 so far has raised $27.2 million in net proceeds through its previously established "at-the-market" equity offering program (the "ATM Program"). The Company currently has capacity to issue additional shares of common stock under this ATM program. Clovis remains focused on its liquidity position and is committed to raising additional capital in the near term in order to fund its operating plan for the next 12 months and beyond.

Clovis also paid off in full at maturity its 2.50% convertible senior notes due 2021. The Company’s next convertible debt maturity is August 1, 2024 and has a conversion price of $7.29 for a portion, and a conversion price of $6.24 for the remainder.

As of December 31, 2021, the Company had drawn $147.2 million under the Sixth Street Partners, LLC (SSP) ATHENA clinical trial financing and had up to $27.8 million available to draw under the agreement to fund the expenses of the ATHENA trial.

Net cash used in operating activities was $41.3 million for 4Q 2021, down from $56.1 million reported in 4Q 2020. Similarly, net cash used in operating activities for FY 2021 was $196.1 million, compared with $252.7 million for FY 2020. Cash burn in Q4 2021 was $31.6 million, down 23% from the Q4 2020 quarter cash burn of $40.9 million. Cash burn for the twelve months ended December 31, 2021 was $148.6 million, down 24% from the twelve months ended 2020 cash burn of $195.6 million.

Clovis Oncology Pipeline Highlights

Three Anticipated Rubraca Phase 3 Studies on Track for 2022 Read-Outs

Top-line data from the ATHENA Phase 3 study in first-line maintenance treatment ovarian cancer setting evaluating Rubraca monotherapy versus placebo (ATHENA-MONO) are expected in the second quarter of 2022 based on a slower than expected event count. Data from the combination arm of Rubraca plus Opdivo (nivolumab) versus Rubraca monotherapy (ATHENA-COMBO) are expected in the fourth quarter of 2022.

Top-line data from the TRITON3 trial, which is expected to serve as the confirmatory study for Rubraca’s approval in metastatic castration-resistant prostate cancer (mCRPC) as well as a potential second-line label expansion, are expected in the second quarter of 2022. TRITON3 is a Phase 3 study evaluating Rubraca versus physician’s choice of chemotherapy or second-line androgen deprivation therapy in patients with mCRPC with BRCA and ATM mutations.

The three anticipated data read-outs, ATHENA-MONO, ATHENA-COMBO and TRITON3, provide the potential to reach larger patient populations in earlier lines of therapy for ovarian and prostate cancers. Beyond the opportunity for monotherapy Rubraca in first-line ovarian cancer, the ATHENA-COMBO study represents the potential to introduce an anti-PD-1-containing regimen for the first time into a broad population of ovarian cancer patients.

The timing for each Phase 3 data read-out is contingent upon the occurrence of the protocol-specified progression-free survival (PFS) events, and timing estimates are based on event-based projections.

LuMIERE Phase 1/2 Study of FAP-2286 Enrolling Patients with FAP-Positive Solid Tumors into Phase 1; Initial Phase 1 LuMIERE Data Expected in 2022

FAP-2286 is the first peptide-targeted radionuclide therapy (PTRT) and imaging agent targeting fibroblast activation protein (FAP) to enter clinical development and is the lead candidate in Clovis Oncology’s TRT development program. The Phase 1 portion of the LuMIERE study, for which enrollment in the second dose cohort is currently ongoing, is evaluating the safety of the FAP-targeting investigational therapeutic agent and will identify the recommended Phase 2 dose and schedule of lutetium-177 labeled FAP-2286 (177Lu-FAP-2286). FAP-2286 labeled with gallium-68 (68Ga-FAP-2286) is being used as an investigational imaging agent to identify patients with FAP-positive tumors appropriate for treatment in LuMIERE. The first presentations of Phase 1 data from LuMIERE are expected at nuclear medicine-focused meetings in 2022. Once the Phase 2 dose is determined, Phase 2 expansion cohorts are planned in multiple tumor types and are expected to initiate in 2022.

For more information about FAP-2286, targeted radionuclide therapy (TRT), or Clovis’ TRT development program, click here.

Conference Call Details

Clovis will hold a conference call this morning, February 23, at 8:30am ET, to discuss Q4 and Full Year 2021 results and provide an update on the Company’s clinical development programs and regulatory and commercial outlook. The conference call will be simultaneously webcast on the Clovis Oncology website at clovisoncology.com, and archived for future review. Dial-in numbers for the conference call are as follows: US participants (888) 440-4615, International participants (646) 960-0682, conference ID: 2259685.

About Rubraca (rucaparib)

Rubraca is an oral, small molecule inhibitor of PARP1, PARP2 and PARP3 being developed in multiple tumor types, including ovarian and prostate cancers, as monotherapy and in combination with other anti-cancer agents. Exploratory studies in other tumor types are also underway. Clovis holds worldwide rights for Rubraca.

In the United States, Rubraca is approved for the maintenance treatment of adult patients with recurrent epithelial, ovarian, fallopian tube, or primary peritoneal cancer who are in a complete or partial response to platinum-based chemotherapy. Rubraca is also approved in the United States for the treatment of adult patients with deleterious BRCA mutation (germline and/or somatic) associated epithelial ovarian, fallopian tube, or primary peritoneal cancer who have been treated with two or more chemotherapies and selected for therapy based on an FDA-approved companion diagnostic for Rubraca. Additionally, Rubraca is approved in the US for the treatment of adult patients with a deleterious BRCA mutation (germline and/or somatic)-associated metastatic castration-resistant prostate cancer (mCRPC) who have been treated with androgen receptor-directed therapy and a taxane-based chemotherapy. Select patients for therapy based on an FDA-approved companion diagnostic for Rubraca. This indication is approved under accelerated approval based on objective response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials. The TRITON3 clinical trial is expected to serve as the confirmatory study for the Rubraca accelerated approval in mCRPC.

In Europe, Rubraca is approved for the maintenance treatment of adults with platinum-sensitive relapsed, high-grade epithelial, ovarian, fallopian tube, or primary peritoneal cancer who are in response (complete or partial) to platinum-based chemotherapy. Rubraca is also approved in Europe for the treatment of adult patients with platinum sensitive, relapsed or progressive, BRCA mutated (germline and/or somatic), high-grade epithelial ovarian, fallopian tube, or primary peritoneal cancer, who have been treated with two or more prior lines of platinum-based chemotherapy, and who are unable to tolerate further platinum-based chemotherapy.

Rubraca is an unlicensed medical product outside the US and Europe.

About FAP-2286

FAP-2286 is a clinical candidate under investigation as a peptide-targeted radionuclide therapy (PTRT) and imaging agent targeting fibroblast activation protein (FAP). FAP-2286 consists of two functional elements: a targeting peptide that binds to FAP and a site that can be used to attach radioactive isotopes for imaging and therapeutic use. High FAP expression has been shown in pancreatic ductal adenocarcinoma, salivary gland, mesothelioma, colon, bladder, sarcoma, squamous non-small cell lung, squamous head and neck cancers, and cancers of unknown primary. High FAP expression was detected in both primary and metastatic tumor samples and was independent of tumor stage or grade. Clovis holds US and global rights for FAP-2286 excluding Europe, Russia, Turkey, and Israel.

FAP-2286 is an unlicensed medical product.

About Targeted Radionuclide Therapy

Targeted radionuclide therapy is an emerging class of cancer therapeutics, which seeks to deliver radiation directly to the tumor while minimizing delivery of radiation to normal tissue. Targeted radionuclides are created by linking radioactive isotopes, also known as radionuclides, to targeting molecules (e.g., peptides, antibodies, small molecules) that can bind specifically to tumor cells or other cells in the tumor environment. Based on the radioactive isotope selected, the resulting agent can be used to image and/or treat certain types of cancer. Agents that can be adapted for both therapeutic and imaging use are known as "theranostics." Clovis is developing a pipeline of novel, targeted radiotherapies for cancer treatment and imaging, including its lead candidate, FAP-2286, an investigational peptide-targeted radionuclide therapeutic (PTRT) and imaging agent, as well as three additional discovery-stage compounds.

On February 23, 2022 BioMarin reported that Fourth Quarter and Full Year 2021 Financial Results and Corporate Updates (Press release, BioMarin, FEB 23, 2022, View Source [SID1234608874]).

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(1) Net Product Revenues Marketed by BioMarin is the sum of revenues from Vimizim, Naglazyme, Kuvan, Palynziq, Brineura and Voxzogo (formerly known as vosoritide) for the three and twelve months ended December 31, 2021, each calculated in accordance with Generally Accepted Accounting Principles in the United States (U.S. GAAP). Sanofi (formally known as Sanofi Genzyme) is BioMarin’s sole customer for Aldurazyme and is responsible for marketing and selling Aldurazyme to third parties. Refer to page 10 for a table showing Net Product Revenues by product. In January 2020, BioMarin divested the Firdapse assets to a third party in a sale transaction. The sale is reflected in the Company’s consolidated financial statements for the twelve months ended December 30, 2020; as a result of the transaction BioMarin no longer recognizes Net Product Revenues from Firdapse.

(2) Not meaningful

(3) Non-GAAP Income is defined by the Company as reported GAAP Net Income/Loss, excluding net interest expense, provision for (benefit from) income taxes, depreciation expense, amortization expense, stock-based compensation expense, contingent consideration expense and, in certain periods, certain other specified items. Refer to Non-GAAP Information beginning on page 11 of this press release for a complete discussion of the Company’s Non-GAAP financial information and reconciliations to the comparable information reported under U.S. GAAP.

BioMarin Pharmaceutical Inc. (NASDAQ: BMRN) (BioMarin or the Company) reported financial results for the fourth quarter and full-year ended December 31, 2021.

BioMarin Announces Fourth Quarter and Full-year 2021 Results
"During 2021, we established the foundation for a return to double-digit revenue growth and profitability in 2022," said Jean-Jacques Bienaimé, Chairman and Chief Executive Officer of BioMarin. "We are pleased with 2021 full-year results, which demonstrated solid performance despite the impact of the loss of exclusivity of Kuvan in the U.S. Following the 2021 global approvals of Voxzogo in the U.S., Europe and Brazil, the enthusiasm from families seeking treatment for their children with achondroplasia has been very encouraging. We are pleased that families now have an approved treatment option, and we look forward to increasing access to Voxzogo as the launch rolls out over the coming quarters."

Mr. Bienaimé continued, "With Voxzogo in launch mode in many countries across the globe, the regulatory team is focused on our next significant potential approval with valoctocogene roxaparvovec gene therapy for the treatment of severe hemophilia A. The two-year data from the 134-participant Phase 3 study, shared in January 2022, met all primary and secondary efficacy endpoints. The results are clinically meaningful, demonstrating superiority to standard of care and an 85% reduction in annualized bleeding rates compared to baseline. We anticipate resubmitting the U.S. application in the second quarter of 2022 and continue to anticipate the European opinion in the second quarter of 2022. With the potential approvals of valoctocogene roxaparvovec in Europe and US, and the continued strong launch of Voxzogo, we expect 2022 to be a transformational year for BioMarin and the patients we seek to serve."

Financial Highlights:

Total Revenues for the fourth quarter of 2021 were $449.8 million, essentially flat compared to the same period in 2020 despite continued erosion of the U.S. Kuvan market. Significant product level revenue fluctuations were as follows:
Higher Aldurazyme product revenues due to timing of product fulfillment to Sanofi. BioMarin Aldurazyme revenues are driven by the timing of when the product is released and control is transferred to Sanofi. Revenues for the fourth quarter of 2021 were comparatively higher than 2020 due to such timing.
Higher Palynziq product revenues primarily due to a combination of revenues from more patients in the U.S. achieving maintenance dosing and new patients initiating therapy. The commercial launch of Palynziq in BioMarin’s European, Middle East and African (EMEA) region continues to progress through individual country level pricing and reimbursement negotiations.
Higher Vimizim product revenues primarily driven by timing of orders in the Middle East and Latin America.
Voxzogo received approval from European Medicines Agency (EMA) and the U.S. Food and Drug Administration (FDA) in the third and fourth quarters of 2021 with commercial sales launching regionally in the same period as approval.
These factors were more than offset by the following:

Lower Naglazyme product revenues primarily driven by timing of orders from Latin America, the Middle East and Europe. High patient compliance rates and year-over-year patient growth reflect strong underlying demand.
Lower Kuvan product revenues primarily due to generic competition as a result of the loss of exclusivity in the U.S., which was consistent with expectations.
GAAP Net Loss increased to $57.9 million for the fourth quarter of 2021 compared to GAAP Net Income of $22.1 million for the same period in 2020 primarily due to the following:
Higher tax benefit in 2020 due to the change in the jurisdictional mix of earnings and the related tax impact from the completion of an intra-entity transfer of certain intellectual property rights to an Irish subsidiary. There was no similar transaction in 2021.
Higher selling, general and administrative (SG&A) expenses primarily due to higher commercialization activities to support the commercial launch of Voxzogo, as well as an increase in administrative costs.
Non-GAAP Income for the fourth quarter of 2021 decreased to $7.1 million compared to Non-GAAP Income of $39.5 million for the same period in 2020. The decrease in Non-GAAP Income for the quarter compared to the same period in 2020 was primarily attributable to higher SG&A and research and development (R&D) expenses.
Late-stage Regulatory Portfolio (Voxzogo and valoctocogene roxaparvovec)

In August 2021, the European Commission approved Voxzogo for the treatment of children, ages 2 years and older. Regulatory approvals were also received in Brazil and the U.S. in November 2021, for children ages five and older with open growth plates. The launch is actively underway, with market access and reimbursement progressing as anticipated. By February 15, 2022, an estimated 210 children were being treated with commercial Voxzogo globally, with an estimated additional 54 children in process in the U.S.
Marketing authorization reviews of Voxzogo are in process in Japan and Australia, with potential approvals in those countries in 2022. At the end of 2021, there were seven active markets contributing to Voxzogo sales.
Today, the Company announced an update from the Phase 2 randomized, double-blind, placebo-controlled Voxzogo study in infants and young children up to five years of age with achondroplasia. 52-week results trended in favor of Voxzogo compared to placebo on height Z-score, annualized growth velocity, with no worsening in proportionality in the overall study population. Height Z-score measures height adjusted for age and sex. The safety profile was generally consistent with older subjects from the Phase 3 Voxzogo 301 study and current label population. Serious Adverse Events (SAEs) were higher in the placebo group (18%) compared to Voxzogo treated children (7%). All SAEs, including a fatal event of SIDS in the treatment group, were deemed by the investigators to be unrelated to treatment. A small increase in events of sleep apnea were reported in the treatment group that were mild or moderate in severity and did not require treatment discontinuation. These events will be fully assessed when sleep study and MRI data are available. BioMarin intends to initiate discussions with regulatory health authorities to discuss next steps regarding efforts to expand access to Voxzogo treatment for this younger age group.
The European Medicines Agency (EMA) validated BioMarin’s Marketing Authorization Applications (MAA) for valoctocogene roxaparvovec resulting in an anticipated Committee for Medicinal Products for Human Use (CHMP) opinion in the second quarter of 2022. BioMarin has provided the EMA with two-year follow-up safety and efficacy data from the GENEr8-1 study.
Based on the favorable results from the two-year follow-up safety and efficacy data from the GENEr8-1 study, BioMarin is targeting a Biologics License Application (BLA) resubmission for valoctocogene roxaparvovec in the second quarter of 2022. If the resubmission satisfies FDA’s response to the Complete Response Letter received in August 2020, BioMarin expects resubmission will be followed by a 6-month review procedure by the FDA.
Earlier-stage Development Portfolio (BMN 307, BMN 255, BMN 331, BMN 351, BMN 349, DiNA-001)

BMN 307 gene therapy product candidate for PKU: In September 2021, the FDA placed a clinical hold on PHEarless, the Phase 1/2 study evaluating BMN 307, an investigational AAV5-phenylalanine hydroxylase (PAH) gene therapy, in adults with phenylketonuria (PKU). The hold was based on pre-clinical study findings from a model designed to understand the durability of BMN 307 activity in mice bearing two germline mutations, one rendering the mice immunodeficient. In February 2022, the FDA requested data from additional non-clinical studies to assess theoretical oncogenic risk to human study participants, which is expected to take several quarters. The Company will communicate next steps for the program when available.
BMN 255 for primary hyperoxaluria type 1, a subset of chronic renal disease: The Investigational New Drug application (IND) for BMN 255 is active and the Company is dosing subjects with dose selection for advanced studies expected in the second half of 2022. BioMarin believes the availability of a potent, orally bioavailable, small molecule like BMN 255, may be able to significantly reduce disease and treatment burden in certain people with chronic renal disease.
BMN 331 gene therapy product candidate for Hereditary Angioedema (HAE): The Company announced that its Phase 1/2 HAERMONY study to evaluate BMN 331, an investigational AAV5-mediated gene therapy for people living with hereditary angioedema (HAE), is open for enrollment. In addition, the FDA granted Orphan Disease Designation status to BMN 331.
BMN 351 for Duchenne Muscular Dystrophy (DMD): IND-enabling studies continue with BMN 351, an antisense oligonucleotide therapy for individuals with 51-skip-amenable DMD. BMN 351 was developed using familiar chemistry and superior biology, by targeting a novel, upstream, splice enhancer site demonstrating improved binding affinity and metabolic stability in preclinical models. Preclinical data suggest that restored expression of near-full-length dystrophin protein at previously achieved levels of up to 40% will convert phenotypes from rapid loss to durable preservation of strength and ambulation. BioMarin expects to file an IND for BMN 351 in the first half of 2022, and anticipates treating clinical trial participants with Duchenne muscular dystrophy in the fourth quarter of 2022.
BMN 349 for alpha-1 antitrypsin deficiency: Preclinical studies have demonstrated that BMN 349 is an orally bioavailable, small molecule that is titratable with rapid onset and high potency and efficacy. Preclinical results have strong implications for potential improvement of current management, particularly around burden of treatment, particularly for severe cases requiring rapid action. BioMarin’s goal is to file the IND in the second half of 2023.
DiNA-001 for MYBPC3 hypertrophic cardiomyopathy (HCM): Preclinical studies are underway with DiNA-001 following a collaboration announced in 2020 with DiNAQOR, a gene therapy platform company, to develop novel gene therapies to treat rare genetic cardiomyopathies. Mutations in MYBPC3 are the most common cause of inherited HCM. Early investigations suggest that gene therapy-mediated gene transfer can lead to widespread expression of the gene product, cardiac myosin-binding protein C (MyBP-C), in cardiac tissue, which can normalize relaxation kinetics and potentially ameliorate the disease phenotype in individuals suffering from cardiomyopathy. BioMarin’s goal is to file the IND in 2023.

(1) All Financial Guidance items are calculated based on U.S. GAAP with the exception of Non-GAAP Income. Refer to Non-GAAP Information beginning on page 11 of this press release for a complete discussion of the Company’s Non-GAAP financial information and reconciliations to the corresponding GAAP reported information.

BioMarin will host a conference call and webcast to discuss fourth quarter and year to date 2021 financial results today, Wednesday, February 23, 2022 at 4:30 p.m. ET. This event can be accessed on the investor section of the BioMarin website at www.biomarin.com.

On February 23, 2022 BioCryst Pharmaceuticals, Inc. (Nasdaq:BCRX) reported financial results for the fourth quarter and full year ended December 31, 2021, and provided a corporate update (Press release, BioCryst Pharmaceuticals, FEB 23, 2022, View Source [SID1234608873]).

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"The successful launch of ORLADEYO, the rapid advancement of our pipeline and the additional capital we acquired last year have transformed BioCryst. With more than $500 million on our balance sheet and ORLADEYO revenue growing to no less than $250 million in 2022, and $1 billion in global peak sales, we are focused on compounding the value of the company by allocating capital to grow ORLADEYO and advancing our complement program to get our oral drugs to patients suffering from many different rare diseases," said Jon Stonehouse, president and chief executive officer of BioCryst.

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 fourth quarter of 2021 was $46.2 million.

New patient demand for ORLADEYO remains strong and consistent, with a similar number of new patients added in Q4 2021 as in each of the previous three quarters of the year. Patients switching from other prophylactic therapies and acute-only therapy continue to drive the launch. More than half of patients new to ORLADEYO since launch had a previous prophylactic medicine prior to ORLADEYO and most of the remainder were from acute-only treatment.

Most patients are well-controlled on ORLADEYO and remain on therapy. Approximately 70 percent of patients starting ORLADEYO, including those switching from injectable prophylaxis, remain on ORLADEYO in the first year.
The ORLADEYO prescriber base continues to grow significantly as physicians gain real-world experience. In market research, 60 U.S. physicians, who treat an average of seven HAE patients each, reported that they expect to double their use of ORLADEYO, and that ORLADEYO will become their most prescribed prophylactic treatment in the next 12 months.

ORLADEYO is now covered by all major payors and pharmacy benefit managers, which will lead to more patients moving quickly to paid product.

ORLADEYO net revenue is expected to benefit from this wide coverage and continued new patient growth throughout 2022. Because of typical first quarter requirements from payors for prescription reauthorization of specialty products, like ORLADEYO, that can temporarily move patients from paid drug to free product, copayment assistance and Medicare D cost sharing dynamics, the company expects little to no ORLADEYO net revenue growth from Q4 2021 to Q1 2022. The company has accounted for this expected Q1 impact in its expectation that full year 2022 ORLADEYO global net revenues will double year over year to no less than $250 million.
"We are excited by the strong start to the ORLADEYO launch and the favorable experience most HAE patients are having controlling their HAE attacks with an oral, once-daily capsule. With a sizeable base of patients already on therapy, reimbursement in place for the full year in 2022, and more face-to-face opportunities for our commercial team to engage directly with patients and physicians, we are looking forward to more than doubling our revenue this year as we continue on our trajectory to become the market leader in HAE prophylaxis," said Charlie Gayer, chief commercial officer of BioCryst.

ORLADEYO: Global Updates

ORLADEYO has been launched in 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

BioCryst is currently enrolling patients in two global pivotal trials, REDEEM-1 and REDEEM-2, with the company’s oral Factor D inhibitor, BCX9930 (500 mg bid), in patients with paroxysmal nocturnal hemoglobinuria (PNH). REDEEM-1 is a randomized, open-label, active, comparator-controlled comparison of the efficacy and safety of BCX9930 monotherapy in approximately 81 PNH patients with an inadequate response to a C5 inhibitor. REDEEM-2 is a randomized, placebo-controlled trial to evaluate the efficacy and safety of BCX9930 as monotherapy versus placebo in approximately 57 PNH patients not currently receiving complement inhibitor therapy. The primary endpoint for both trials is the change from baseline in hemoglobin, assessed at weeks 12 to 24 in REDEEM-1 and at week 12 in REDEEM-2.

The company also has begun patient enrollment for RENEW, a proof-of-concept (PoC) basket trial of oral BCX9930 (500 mg bid) in complement-mediated renal diseases. The trial is being conducted in patients with C3 glomerulopathy (C3G), IgA nephropathy (IgAN), and primary membranous nephropathy (PMN).
BioCryst plans to further advance and expand its Factor D program over the next two years by achieving the following by the end of 2023:

Complete and report data from REDEEM-1 and REDEEM-2
Prepare to submit regulatory approval filings in PNH
Complete the renal PoC basket trial and advance to pivotal trials in C3G, IgAN and PMN
Commence PoC trials in other complement-mediated diseases
Additional Updates

On November 22, 2021, the company announced financing transactions totaling $350 million in new funding for BioCryst from Royalty Pharma and OMERS Capital Markets.

On November 1, 2021, the company announced the appointment of Jinky Ang Rosselli as Chief Data and Insights Officer.
Fourth Quarter 2021 Financial Results

For the three months ended December 31, 2021, total revenues were $47.2 million, compared to $4.0 million in the fourth quarter of 2020. The increase was primarily due to $46.2 million in ORLADEYO net revenue in the fourth quarter of 2021.

Research and development (R&D) expenses for the fourth quarter of 2021 increased to $63.5 million from $35.4 million in the fourth quarter of 2020, primarily due to increased investment in the development of our Factor D program and other research, preclinical and development costs, offset by a slight reduction in spend on the ORLADEYO program following our commercial launch in December 2020.

Selling, general and administrative (SG&A) expenses for the fourth quarter of 2021 increased to $35.4 million, compared to $21.0 million in the fourth quarter of 2020. The increase was primarily due to increased investment to support the commercial launch of ORLADEYO and expanded international operations.

Interest expense was $18.8 million in the fourth quarter of 2021, compared to $5.6 million in the fourth quarter of 2020. The increase was due to service on the royalty and debt financings, which were completed in December 2020 and November 2021.

A one-time non-cash gain of $55.8 million related to the extinguishment of debt was recognized during the fourth quarter of 2021 to write-off the non-recourse PhaRMA Notes and related accrued interest payable.

Net loss for the fourth quarter of 2021 was $17.8 million, or $0.10 per share, compared to a net loss of $60.5 million, or $0.34 per share, for the fourth quarter of 2020. Non-GAAP net loss for the fourth quarter of 2021 was $73.6 million, or $0.40 per share when excluding the one-time non-cash gain on the extinguishment of the non-recourse PhaRMA Notes. A reconciliation between GAAP and non-GAAP net loss is provided in the table below.

Cash, cash equivalents, restricted cash and investments totaled $517.8 million as of December 31, 2021, compared to $302.6 million as of December 31, 2020. Operating cash use for the fourth quarter of 2021 was $29.0 million.

Full Year 2021 Financial Results

For the full year ended December 31, 2021, total revenues were $157.2 million, compared to $17.8 million in the full year ended December 31, 2020. The increase was primarily due to $122.6 million of ORLADEYO net revenue following our commercial launch in December 2020, recognition of a $15.0 million milestone payment from Torii related to the Japanese National Health Insurance System approval of ORLADEYO in Japan, and increased RAPIVAB revenues. These increases in revenue were partially offset by a reduction in royalty revenue (excluding those associated with ORLADEYO sales) of $4.2 million, a reduction in contract revenue of $3.3 million and the recognition of $1.9 million of deferred revenue in the prior year period compared to none in the current year period.

R&D expenses in full year 2021 increased to $208.8 million from $123.0 million in full year 2020, primarily due to increased investment in our Factor D program, and an increase in other research, preclinical and development activities, partially offset by a ramp down of clinical investment related to ORLADEYO, which launched commercially in the U.S. during December 2020.

SG&A expenses in full year 2021 increased to $118.8 million, compared to $67.9 million in full year 2020. The increase was primarily due to increased investment to support the U.S. commercial launch of ORLADEYO and expanded international operations.

Interest and other income was $0.1 million in full year 2021, compared to $9.4 million in full year 2020. The decrease was primarily due to the one-time settlement of arbitration proceedings related to our Seqirus dispute in the first quarter of 2020.

Interest expense was $59.3 million in full year 2021, compared to $14.5 million in full year 2020. The increase was associated with the $125.0 million Term A Loan under the Credit Agreement and Royalty financing obligations which were completed in December 2020 and November 2021.

A one-time non-cash gain of $55.8 million on extinguishment of debt was recognized in the full year 2021 related to the write-off of the non-recourse PhaRMA notes and related accrued interest payable.

Net loss for full year 2021 was $184.1 million, or $1.03 per share, compared to a net loss of $182.8 million, or $1.09 per share, for full year 2020. Non-GAAP net loss for full year 2021 was $239.9 million, or $1.34 per share when excluding the one-time gain on the extinguishment of the non-recourse PhaRMA Notes. A reconciliation between GAAP and non-GAAP net loss is provided in the table below.

Non-GAAP Pro forma Financial Measures

The information furnished in this release includes non-GAAP pro forma financial measures that differ from measures calculated in accordance with generally accepted accounting principles in the United States of America ("GAAP"), including financial measures labeled as "non-GAAP" or "adjusted."

We believe providing these non-GAAP measures, which show our pro forma results with these items adjusted, is valuable and useful since they allow the company and investors to better understand the company’s financial performance in the absence of these one-time events and will allow investors to more accurately understand our 2021 results and more easily compare them to future results. These non-GAAP pro forma measures also correspond with the way we expect Wall Street analysts to compare our results. Our non-GAAP pro forma measures should be considered only as supplements to, and not as substitutes for or in isolation from, our other measures of financial information prepared in accordance with GAAP, such as GAAP revenue, operating income, net income, and earnings per share.

Our references to our fourth quarter 2021 "non-GAAP pro forma" financial measures of adjusted net loss and adjusted earnings per share constitute non-GAAP financial measures. They refer to our GAAP results, adjusted to show the results without the one-time gain realized by the extinguishment of the debt from our PhaRMA notes.

Financial Outlook for 2022

Based on the strength of the ORLADEYO launch, and continued 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. Operating expenses for full year 2022, not including non-cash stock compensation, are expected to be in the range of $440 million to $480 million. The increase year over year is predominantly driven by additional investment in advancing the Factor D program across multiple indications.

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 # 6365545. 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 # 6365545.