On May 9, 2022 OPKO Health, Inc. (NASDAQ: OPK) reported business highlights and financial results for the three months ended March 31, 2022 (Press release, Opko Health, MAY 9, 2022, View Source [SID1234613922]).

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Business Highlights

Business highlights for the first quarter of 2022 and subsequent weeks include the following:

Acquired ModeX Therapeutics, Inc. (ModeX), gains proprietary immunotherapy technology, new executives and Directors. ModeX is a privately held biotechnology company focused on developing innovative multi-specific immune therapies for cancer and infectious diseases. In connection with the acquisition, Dr. Elias Zerhouni joins OPKO as President and Vice Chairman of the Board of Directors, Dr. Gary Nabel joins as Chief Innovation Officer and a member of OPKO’s Board of Directors, and Alexis Borisy joins OPKO’s Board. OPKO acquired ModeX for $300 million in OPKO common stock.

Completed sale of GeneDx LLC (formerly GeneDx, Inc.) to Sema4 Holdings Corp. (Sema4). Sema4 acquired GeneDx for an upfront payment of $150 million in cash, subject to adjustments, plus 80 million shares of Sema4 Class A common stock, with up to an additional $150 million in revenue-based milestones over the next two years (payable in cash or Sema4 shares at Sema4’s discretion). Based on the closing price of Sema4’s Class A common stock on April 29, 2022, the date the transaction closed, the total upfront consideration is approximately $322 million and the total aggregate consideration including potential milestones is approximately $472 million.

Pfizer launched NGENLA (Somatrogon) injection in Germany, Japan and additional markets. NGENLA was granted marketing authorization by the Ministry of Health, Labour and Welfare in Japan and by the European Commission in January and February of this year, respectively. With the achievement of these milestones, OPKO earned an aggregate of $85 million in milestone payments. NGENLA is a once-weekly injection to treat pediatric patients with growth disturbance due to insufficient secretion of growth hormone. NGENLA provides pediatric patients, their caregivers and healthcare providers with a new treatment option for growth hormone deficiency that reduces the frequency of required injections from once-daily to once-weekly. Pfizer is OPKO’s global commercial partner for Somatrogon.

Vifor Fresenius Medical Care Renal Pharma (VFMCRP) launched RAYALDEE in Germany, and subsequently in Switzerland. VFMCRP initiated the commercial launch of RAYALDEE (extended-release calcifediol) in Germany, the first launch of RAYALDEE outside the U.S. VFMCRP is OPKO’s commercial partner for RAYALDEE in Europe and selected markets outside the U.S. VFMCRP has received marketing authorizations for RAYALDEE in 11 European countries and expects to launch the product in additional markets.
First Quarter Financial Results

Diagnostics: Revenue from services in the first quarter of 2022 was $286.6 million compared with $507.0 million in the prior-year period, with the decrease primarily due to lower COVID-19 testing volume and related reimbursement, partially offset by an improvement in genomic test reimbursement and an increase in clinical and genomic test volumes. BioReference processed approximately 2.0 million COVID-19 PCR tests in the first quarter of 2022 versus 4.1 million in the first quarter of 2021. Total costs and expenses were $330.1 million in the first quarter of 2022 compared with $439.9 million in the first quarter of 2021, resulting in an operating loss of $43.5 million compared with operating income of $67.0 million in the 2021 period. Operating income decreased primarily due to a decline in the volume of COVID-19 tests.

Pharmaceuticals: Revenue from products in the first quarter of 2022 increased to $36.6 million from $33.9 million in the first quarter of 2021, with the increase primarily attributable to accelerating growth of OPKO’s international pharmaceutical businesses. Revenue from sales of RAYALDEE in the first quarter of 2022 was $5.1 million compared with $5.8 million in the prior-year period. Revenue from the transfer of intellectual property was $6.0 million in the first quarter of 2022 compared with $4.3 million in the 2021 period. During the first quarter of 2022, OPKO recognized a $3.0 million sales milestone from VFMCRP triggered by the first commercial sales in Europe. Total costs and expenses were $60.7 million in the first quarter of 2022 compared with $57.4 million in the prior-year period. The increase was driven by the amortization of NGENLA, which received approval in Europe and Japan during the first quarter of 2022, offset by a reduction in inventory reserve, legal expenses and selling expenses related to RAYALDEE. In addition, research and development expenses decreased reflecting reduced spending on the NGENLA development program. The operating loss was $18.1 million in the first quarter of 2022 compared with an operating loss of $19.2 million in the first quarter of 2021.

Consolidated: Consolidated total revenues for the first quarter of 2022 were $329.2 million compared with $545.2 million for the comparable period of 2021. Operating loss for the first quarter of 2022 was $72.4 million compared with operating income of $38.5 million for the 2021 quarter. Net loss for the first quarter of 2022 was $55.4 million, or $0.08 per share, compared with net income of $31.1 million, or $0.05 per diluted share, for the 2021 quarter.

Cash and equivalents: Cash and cash equivalents were $102.3 million as of March 31, 2022. In addition, OPKO has $64.8 million available under its line of credit with JP Morgan. Subsequent to the close of the quarter, OPKO received $150 million gross proceeds from the sale of GeneDx to Sema4. Also, OPKO expects to receive $85 million in milestone payments from Pfizer during the second quarter of 2022.
CONFERENCE CALL & WEBCAST INFORMATION

OPKO’s senior management will provide a business update, discuss first quarter financial results and the ModeX acquisition, and answer questions during a conference call and live audio webcast today beginning at 4:30 p.m. Eastern time. Participants are encouraged to pre-register for the conference call using this link. Callers who pre-register will be given a unique PIN to gain immediate access to the call and bypass the live operator. Those unable to pre-register may participate by dialing (866) 777-2509 (U.S.) or (412) 317-5413 (International). A webcast of the call may also be accessed at OPKO’s Investor Relations page and here.

A telephone replay will be available until May 16, 2022 by dialing (877) 344-7529 (U.S.) or (412) 317-0088 (International) and providing the passcode 6587528. A webcast replay will be available beginning approximately one hour after the completion of the live conference call here.

On May 9, 2022 CRISPR Therapeutics (Nasdaq: CRSP), a biopharmaceutical company focused on creating transformative gene-based medicines for serious diseases, reported financial results for the first quarter ended March 31, 2022 (Press release, CRISPR Therapeutics, MAY 9, 2022, View Source [SID1234613921]).

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"I am pleased with the ongoing momentum across our broad portfolio of innovative gene therapy candidates and anticipate important company milestones in 2022. Alongside our partner Vertex, we remain on track to submit global regulatory filings for CTX001 in late 2022 and have dosed more than 75 patients across both trials to date. We have also initiated two new Phase 3 trials of CTX001 in pediatric patients with TDT and SCD," said Samarth Kulkarni, Ph.D., Chief Executive Officer of CRISPR Therapeutics. "We are also advancing our wholly-owned immuno-oncology pipeline, with new updates expected this year. In addition, enrollment and dosing continues in the Phase 1 clinical trial of VCTX210 for T1D with our partner, ViaCyte. We believe we are well positioned and well capitalized to advance our pipeline and platform to develop transformative medicines for patients suffering from serious diseases."

Recent Highlights and Outlook

Beta Thalassemia and Sickle Cell Disease

Following the completion of enrollment in the ongoing Phase 3 clinical trials for CTX001 in transfusion-dependent beta thalassemia (TDT) and severe sickle cell disease (SCD), announced last quarter, more than 75 patients across both trials have been dosed to date. CRISPR Therapeutics and Vertex anticipate presenting updated data from the clinical trials, with more patients and longer follow-up, at medical conferences in 2022.

CRISPR Therapeutics and Vertex have initiated two new Phase 3 studies of CTX001 in pediatric patients with TDT and SCD.

The companies anticipate submitting global regulatory filings for CTX001 in TDT and SCD in late 2022.

Immuno-Oncology Programs

CRISPR Therapeutics continues to enroll and dose patients in the pivotal trial of CTX110, its wholly-owned allogeneic chimeric antigen receptor T cell (CAR-T) investigational therapy targeting CD19+ B-cell malignancies. The Company expects to report additional data in 2022.

CRISPR Therapeutics’ Phase 1 clinical trials for CTX-120, its wholly-owned allogeneic CAR-T investigational therapy targeting B-cell maturation antigen for the treatment of relapsed or refractory multiple myeloma, and CTX130, its wholly-owned allogeneic CAR-T investigational therapy targeting CD70 for the treatment of both solid tumors and certain hematologic malignancies, are ongoing. Each trial is assessing safety and efficacy of several dose levels. The Company expects to provide updates from each trial in the first half of 2022.

Regenerative Medicine and In Vivo Programs

Enrollment and dosing are ongoing in the Phase 1 clinical trial of VCTX210 for the treatment of type 1 diabetes (T1D). VCTX210 is an investigational, allogeneic, gene-edited, stem cell-derived product developed in collaboration by applying CRISPR Therapeutics’ gene-editing technology to ViaCyte’s proprietary stem cell capabilities for the generation of pancreatic cells designed to evade recognition by the immune system. This immune-evasive cell replacement therapy is designed to enable patients to produce their own insulin.

Based upon ongoing progress with its in vivo approaches for liver gene editing utilizing both viral and non-viral delivery vehicles, CRISPR Therapeutics continues to expect to move multiple programs utilizing in vivo approaches into the clinic in the next 18 to 24 months.

Other Corporate Matters

In April, CRISPR Therapeutics proposed to elect Maria Fardis, Ph.D., MBA, to its Board of Directors at the Company’s upcoming annual general meeting of shareholders to be held later this year. The Company believes her extensive leadership in scaling companies and bringing novel therapies to patients will be an invaluable asset to CRISPR Therapeutics.

In April, CRISPR Therapeutics and Nkarta, Inc. presented preclinical data focused on its natural killer cell platform and pipeline at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2022. The data shows that CD70/CISH/CBLB triple KO CD70-CAR NK cells demonstrated enhanced anti-tumor activity against relevant solid tumor cell lines and provided greater resistance to tumor microenvironment inhibition. These data support the further exploration of CD70/CISH/CBLB triple gene knockout CD70 CAR NK cells for clinical application.

In April, CRISPR Therapeutics was awarded the 2022 Facility of the Year Category Award (FOYA) for Innovation by the International Society for Pharmaceutical Engineering (ISPE) for its state-of-the art manufacturing facility in Framingham, Massachusetts, USA. ISPE’s Facility of the Year Awards program is the premier global awards program recognizing innovation and creativity in the pharmaceutical and biotechnology manufacturing industries. Projects selected for recognition set the standard by demonstrating excellence in facility design, construction, and operations.
First Quarter 2022 Financial Results

Cash Position: Cash, cash equivalents and marketable securities were $2,221.3 million as of March 31, 2022, compared to $2,379.1 million as of December 31, 2021. The decrease in cash of $157.8 million was primarily driven by cash used in operating activities to support ongoing research and development of the Company’s clinical and pre-clinical programs.

Revenue: Total collaboration revenue was $0.2 million for the first quarter of 2022 and 2021.

R&D Expenses: R&D expenses were $118.2 million for the first quarter of 2022, compared to $70.6 million for the first quarter of 2021. The increase in expense was driven by development activities supporting the advancement of our wholly-owned immuno-oncology programs, as well as expenses related to our new U.S. research and development headquarters.

G&A Expenses: General and administrative expenses were $28.0 million for the first quarter of 2022, compared to $24.5 million for the first quarter of 2021. The increase in general and administrative expenses was primarily driven by headcount-related expense.

Collaboration Expense: Collaboration expense, net, was $30.6 million for the first quarter of 2022, compared to $19.9 million for the first quarter of 2021. The increase in collaboration expense, net, was primarily driven by increased pre-commercial and manufacturing scale-up costs associated with our hemoglobinopathies programs under our collaboration with Vertex.

Net Loss: Net loss was $179.2 million for the first quarter of 2022, compared to a net loss of $113.2 million for the first quarter of 2021.
About CTX001
CTX001 is an investigational, autologous, ex vivo CRISPR/Cas9 gene-edited therapy that is being evaluated for patients suffering from TDT or severe SCD, in which a patient’s hematopoietic stem cells are edited to produce high levels of fetal hemoglobin (HbF; hemoglobin F) in red blood cells. HbF is a form of the oxygen-carrying hemoglobin that is naturally present at birth, which then switches to the adult form of hemoglobin. The elevation of HbF by CTX001 has the potential to alleviate or eliminate transfusion requirements for patients with TDT and reduce or eliminate painful and debilitating sickle crises for patients with SCD. Earlier results from these ongoing trials were published as a Brief Report in The New England Journal of Medicine in January of 2021.

Based on progress in this program to date, CTX001 has been granted Regenerative Medicine Advanced Therapy (RMAT), Fast Track, Orphan Drug, and Rare Pediatric Disease designations from the U.S. Food and Drug Administration (FDA) for both TDT and SCD. CTX001 has also been granted Orphan Drug Designation from the European Commission, as well as Priority Medicines (PRIME) designation from the European Medicines Agency (EMA), for both TDT and SCD.

Among gene-editing approaches being investigated/evaluated for TDT and SCD, CTX001 is the furthest advanced in clinical development.

About the CRISPR-Vertex Collaboration
Vertex and CRISPR Therapeutics entered into a strategic research collaboration in 2015 focused on the use of CRISPR/Cas9 to discover and develop potential new treatments aimed at the underlying genetic causes of human disease. CTX001 represents the first potential treatment to emerge from the joint research program. Under a recently amended collaboration agreement, Vertex will lead global development, manufacturing and commercialization of CTX001 and split program costs and profits worldwide 60/40 with CRISPR Therapeutics.

About CLIMB-111
The ongoing Phase 1/2 open-label trial, CLIMB-Thal-111, is designed to assess the safety and efficacy of a single dose of CTX001 in patients ages 12 to 35 with TDT. The trial will enroll up to 45 patients and follow patients for approximately two years after infusion. Each patient will be asked to participate in a long-term follow-up trial.

About CLIMB-121
The ongoing Phase 1/2 open-label trial, CLIMB-SCD-121, is designed to assess the safety and efficacy of a single dose of CTX001 in patients ages 12 to 35 with severe SCD. The trial will enroll up to 45 patients and follow patients for approximately two years after infusion. Each patient will be asked to participate in a long-term follow-up trial.

About CLIMB-131
This is a long-term, open-label trial to evaluate the safety and efficacy of CTX001 in patients who received CTX001 in CLIMB-111 or CLIMB-121. The trial is designed to follow participants for up to 15 years after CTX001 infusion.

About CTX110
CTX110, a wholly owned program of CRISPR Therapeutics, is a healthy donor-derived gene-edited allogeneic CAR-T investigational therapy targeting cluster of differentiation 19, or CD19. CTX110 is being investigated in the ongoing CARBON trial. CTX110 has been granted Regenerative Medicine Advanced Therapy designation from the FDA.

About CARBON
The ongoing Phase 1 single-arm, multi-center, open label clinical trial, CARBON, is designed to assess the safety and efficacy of several dose levels of CTX110 for the treatment of relapsed or refractory B-cell malignancies.

About CTX120
CTX120, a wholly-owned program of CRISPR Therapeutics, is a healthy donor-derived gene-edited allogeneic CAR-T investigational therapy targeting B-cell maturation antigen, or BCMA. CTX120 is being investigated in an ongoing Phase 1 single-arm, multi-center, open-label clinical trial designed to assess the safety and efficacy of several dose levels of CTX120 for the treatment of relapsed or refractory multiple myeloma. CTX120 has been granted Orphan Drug designation from the FDA.

About CTX130
CTX130, a wholly-owned program of CRISPR Therapeutics, is a healthy donor-derived gene-edited allogeneic CAR-T investigational therapy targeting cluster of differentiation 70, or CD70, an antigen expressed on various solid tumors and hematologic malignancies. CTX130 is being developed for the treatment of both solid tumors, such as renal cell carcinoma, and T-cell and B-cell hematologic malignancies. CTX130 is being investigated in two ongoing independent Phase 1, single-arm, multi-center, open-label clinical trials that are designed to assess the safety and efficacy of several dose levels of CTX130 for the treatment of relapsed or refractory renal cell carcinoma and various subtypes of lymphoma, respectively. CTX120 has been granted Orphan Drug designation for the treatment of T-cell lymphoma from the FDA.

About VCTX210
VCTX210 is an investigational, allogeneic, gene-edited, immune-evasive, stem cell-derived therapy for the treatment of type 1 diabetes (T1D). VCTX210 is being developed under a co-development and co-commercialization agreement between CRISPR Therapeutics and ViaCyte, Inc.

On May 9, 2022 ORIC Pharmaceuticals, Inc. (Nasdaq: ORIC), a clinical stage oncology company focused on developing treatments that address mechanisms of therapeutic resistance, reported financial results and operational updates for the quarter ended March 31, 2022 (Press release, ORIC Pharmaceuticals, MAY 9, 2022, View Source [SID1234613920]).

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"We continue to make steady progress in advancing our pipeline of novel oncology candidates," said Jacob M. Chacko, MD, chief executive officer, "We expect to report initial data from our three ongoing studies in the first half of 2023, which includes our Phase 1b single agent trials for ORIC-533, our orally bioavailable CD73 inhibitor, ORIC-114, our brain penetrant EGFR/HER2 inhibitor, and ORIC-944, our embryonic ectoderm development (EED) inhibitor."

First Quarter 2022 and Other Recent Highlights

Preclinical Data Presented at AACR (Free AACR Whitepaper): In April 2022, ORIC disclosed new preclinical data in three poster presentations and one oral presentation at the 2022 American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting.

ORIC-533: Oral Small Molecule CD73 Inhibitor
ORIC-533 is a highly potent, orally bioavailable small molecule inhibitor of CD73 that has demonstrated more potent adenosine inhibition in preclinical studies compared to an antibody approach and other small molecule inhibitors of the adenosine pathway. In preclinical studies, ORIC-533 overcame immune suppression and triggered significant lysis and cell death of multiple myeloma cells in an assay comprised of autologous bone marrow microenvironment. A Phase 1b trial with ORIC-533 as a single agent in multiple myeloma is enrolling patients, and the company expects to report initial Phase 1b data from this trial in the first half of 2023.

ORIC-114: EGFR/HER2 Inhibitor
ORIC-114 is a brain penetrant, orally bioavailable, irreversible inhibitor designed to selectively target EGFR and HER2 with high potency against exon 20 insertion mutations. In preclinical studies, ORIC-114 achieved tumor regressions in an EGFR exon 20 NSCLC model with superior efficacy relative to CLN-081 and demonstrated greater anti-tumor activity compared to mobocertinib (TAK-788) in an intracranial NSCLC model. A Phase 1b trial with ORIC-114 as a single agent is enrolling patients with advanced solid tumors with EGFR or HER2 exon 20 alterations or HER2 amplification and allows for patients with CNS metastases that are either treated or untreated but asymptomatic. The company expects to report initial Phase 1b data from this trial in the first half of 2023.

ORIC-944: PRC2 Inhibitor
ORIC-944 is a potent and selective allosteric inhibitor of polycomb repressive complex 2 (PRC2) that targets its regulatory embryonic ectoderm development (EED) subunit and has demonstrated single agent efficacy in multiple enzalutamide-resistant prostate cancer models in preclinical studies. A Phase 1b trial with ORIC-944 as a single agent is enrolling patients with metastatic prostate cancer, and the company expects to report initial Phase 1b data from this trial in the first half of 2023.

PLK4 Inhibitor Program
In March, the company announced a small molecule therapeutic program intended to address a mechanism of innate resistance found in a subset of breast cancers, specifically a synthetic lethal interaction of polo-like kinase 4 (PLK4) inhibition in tumors bearing a TRIM37 DNA amplification. ORIC discovered novel, potent, orally bioavailable small molecule inhibitors of PLK4 that are highly selective and achieved strong anti-tumor activity of TRIM37 high xenograft tumors, with corresponding pharmacodynamic effects and no body weight loss. The PLK4 inhibitor program is currently in lead optimization.

Anticipated Program Milestones

ORIC anticipates the following upcoming milestones:

ORIC-533: Initial Phase 1b data in 1H 2023
ORIC-114: Initial Phase 1b data in 1H 2023
ORIC-944: Initial Phase 1b data in 1H 2023
First Quarter 2022 Financial Results

Cash, Cash Equivalents and Investments: Cash, cash equivalents and investments totaled $256.2 million as of March 31, 2022, which the company expects will fund its current operating plan into the second half of 2024.
R&D Expenses: Research and development (R&D) expenses were $16.8 million for the three months ended March 31, 2022, compared to $11.7 million for the same period in 2021, an increase of $5.1 million. The increase was primarily driven by an increase in external expenses related to the advancement of ORIC-533, ORIC-114, ORIC-944 and our other product candidates of $4.6 million, offset by a decrease in ORIC-101 costs of $0.7 million due to the discontinuation of the program in the first quarter of 2022. Higher internal expenses related to higher personnel costs, including additional non-cash stock-based compensation of $0.5 million, also contributed to the increase in research and development expenses.
G&A Expenses: General and administrative (G&A) expenses were $6.4 million for the three months ended March 31, 2022, compared to $4.9 million for the same period in 2021, an increase of $1.6 million. The increase was primarily due to higher personnel costs, including additional non-cash stock-based compensation of $0.7 million.

On May 9, 2022 Heron Therapeutics, Inc. (Nasdaq: HRTX), a commercial-stage biotechnology company focused on improving the lives of patients by developing and commercializing therapeutic innovations that improve medical care, reported financial results for the three months ended March 31, 2022 and highlighted recent corporate updates (Press release, Heron Therapeutics, MAY 9, 2022, View Source [SID1234613919]).

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Recent Corporate Updates

Acute Care Franchise

ZYNRELEF:

The ZYNRELEF (bupivacaine and meloxicam) extended-release solution New Drug Application (NDA) was approved by the U.S. Food and Drug Administration (FDA) in May 2021. In December 2021, the FDA approved our supplemental New Drug Application (sNDA) for ZYNRELEF, now covering approximately 7 million procedures annually. ZYNRELEF is currently indicated for use in adults for soft tissue or periarticular instillation to produce postsurgical analgesia for up to 72 hours after foot and ankle, small-to-medium open abdominal, and lower extremity total joint arthroplasty surgical procedures. The FDA also agreed to the contents of a second sNDA, planned for later this year, designed to further expand the indication statement.

ZYNRELEF net product sales for the three months ended March 31, 2022 were $1.1 million, which was net of $0.3 million in returns of short-dated ZYNRELEF and a continued reduction of initial distribution channel inventory. Short-dated product returns were due to delays in obtaining initial FDA approval of ZYNRELEF.

ZYNRELEF end-user (ambulatory surgical centers (ASC) and hospitals) demand units’ sales were 8,673 in the first quarter of 2022, representing an increase of 68% over the prior quarter.

During the first three quarters of commercial launch ended March 31, 2022, over 450 unique accounts purchased ZYNRELEF with 80% of those accounts reordering the product.

As of April 30, 2022, ZYNRELEF has received 319 formulary approvals, with over a 90% hospital approval rate, and an estimated 68% of formulary approvals have been for unrestricted use. Over 60 additional formulary review meetings are scheduled through June 30, 2022.

Effective April 1, 2022, ZYNRELEF became the only local anesthetic separately reimbursed for Medicare patients in the Hospital Outpatient Department (HOPD) setting of care under a 3-year transitional pass-through status. Multiple commercial and Medicaid payers covering over 120 million lives have agreed to reimburse ZYNRELEF outside of the surgical bundle payment for surgeries performed in ASCs, with many of these covered lives also having their hospital outpatient procedures reimbursed outside the surgical bundle payment. Commercial and Medicaid payers represent more than 80% of our target patients in the outpatient setting. On November 2, 2021, we were issued a specific C-code (C9088) for separate reimbursement in the ASC setting of care effective January 1, 2022.

In March 2022, Health Canada issued a Notice of Compliance to commercialize ZYNRELEF for instillation into the surgical wound for postoperative analgesia after bunionectomy, open inguinal herniorrhaphy, and total knee arthroplasty surgical procedures. Based on prior agreements with the FDA, Heron already has clinical studies underway, which we plan to submit to Health Canada to expand the indication statement. Heron is currently in partnering discussions related to Canada and other countries outside the U.S.
NDA Submission for HTX-019 for Prevention of PONV in Adults Under Review: A 505(b)(2) NDA for HTX-019 for the prevention of postoperative nausea and vomiting (PONV) in adults was submitted to the FDA in November 2021. The FDA accepted the NDA for filing and set a Prescription Drug User Fee Act (PDUFA) goal date of September 17, 2022.
Oncology Care Franchise

2022 Oncology Care Franchise Net Product Sales: For the three months ended March 31, 2022, oncology care franchise net product sales were $22.4 million, compared to $20.0 million for the same period in 2021. During the first quarter, Heron’s oncology care franchise net product sales grew by 13% over the prior quarter with continued moderate growth expected for the remainder of 2022.

CINVANTI Net Product Sales: Net product sales of CINVANTI (aprepitant) injectable emulsion for the three months ended March 31, 2022 were $20.3 million, compared to $18.5 million for the same period in 2021.

SUSTOL Net Product Sales: Net product sales of SUSTOL (granisetron) extended-release injection for the three months ended March 31, 2022 were $2.1 million, compared to $1.5 million for the same period in 2021.

2022 Oncology Care Franchise Net Product Sales Guidance: Heron currently expects the second quarter of 2022 net product sales for the oncology care franchise in the range of $22 million to $23 million, with full-year 2022 net product sales for the oncology care franchise in the range of $89 million to $93 million.
"Although the start of the first quarter was challenging due to the COVID-19 pandemic, in the last few months ZYNRELEF has gained momentum following the FDA approval of the expanded indications. We expect continued strong growth in the current quarter with the receipt of pass-through status from CMS for HOPD, as evidenced by an 85% increase in demand units in the first month of the second quarter versus the first month of the first quarter," said Barry Quart, Pharm.D., Chairman and Chief Executive Officer of Heron. "In oncology care, our CINV portfolio continues to perform well and we look forward to achieving net product sales of $22 million to $23 million in the second quarter of 2022 and full year 2022 net product sales of $89 million to $93 million."

Financial Results

Net product sales for the three months ended March 31, 2022 were $23.5 million, compared to $20.0 million for the same period in 2021.

Heron’s net loss for the three months ended March 31, 2022 was $63.9 million, or $0.63 per share, compared to $52.6 million, or $0.58 per share, for the same period in 2021. Net loss for the three months ended March 31, 2022 included non-cash, stock-based compensation expense of $10.9 million, compared to $11.5 million for the same period in 2021.

As of March 31, 2022, Heron had cash, cash equivalents and short-term investments of $111.9 million, compared to $157.6 million as of December 31, 2021. Net cash used for operating activities for the three months ended March 31, 2022 was $43.9 million, compared to $41.9 million for the same period in 2021. The increase in our net cash used for operating activities was primarily due to changes in working capital related to the launch of ZYNRELEF, including manufacturing of commercial inventory, and an increase in net loss. We expect net cash used for operating activities of $37 million to $39 million in the second quarter of 2022.

Conference Call and Webcast

Heron will host a conference call and webcast on May 9, 2022 at 4:30 p.m. ET. The conference call can be accessed by dialing 1-844-825-9789 for domestic callers and 1-412-317-5180 for international callers. Please provide the operator with the passcode 10166891 to join the conference call. The conference call will also be available via webcast under the Investor Relations section of Heron’s website at www.herontx.com. An archive of the teleconference and webcast will also be made available on Heron’s website for 60 days following the call.

About ZYNRELEF for Postoperative Pain

ZYNRELEF is the first and only dual-acting local anesthetic that delivers a fixed-dose combination of the local anesthetic bupivacaine and a low dose of nonsteroidal anti-inflammatory drug meloxicam. ZYNRELEF is the first and only extended-release local anesthetic to demonstrate in Phase 3 studies significantly reduced pain and significantly increased proportion of patients requiring no opioids through the first 72 hours following surgery compared to bupivacaine solution, the current standard-of-care local anesthetic for postoperative pain control. ZYNRELEF was initially approved by the FDA in May 2021 for use in adults for soft tissue or periarticular instillation to produce postsurgical analgesia for up to 72 hours after bunionectomy, open inguinal herniorrhaphy and total knee arthroplasty. In December 2021, the FDA approved an expansion of ZYNRELEF’s indication. ZYNRELEF is now indicated in the U.S. in adults for soft tissue or periarticular instillation to produce postsurgical analgesia for up to 72 hours after foot and ankle, small-to-medium open abdominal, and lower extremity total joint arthroplasty surgical procedures. Safety and efficacy have not been established in highly vascular surgeries, such as intrathoracic, large multilevel spinal, and head and neck procedures. In September 2020, the European Commission granted a marketing authorization for ZYNRELEF for the treatment of somatic postoperative pain from small- to medium-sized surgical wounds in adults. As of January 1, 2021, ZYNRELEF is approved in 31 European countries including the countries of the European Union and European Economic Area and the United Kingdom. In March 2022, Health Canada issued a Notice of Compliance for ZYNRELEF for instillation into the surgical wound for postoperative analgesia after bunionectomy, open inguinal herniorrhaphy, and total knee arthroplasty surgical procedures.

Please see full prescribing information, including Boxed Warning, at www.ZYNRELEF.com.

About HTX-019 for PONV

HTX-019 is an IV injectable emulsion formulation designed to directly deliver aprepitant, the active ingredient in EMEND (aprepitant) capsules, which is the only substance P/neurokinin-1 (NK1) receptor antagonist (RA) to be approved in the U.S. for the prevention of PONV in adults. The FDA-approved dose of oral EMEND is 40 mg for PONV prevention, which is given within 3 hours prior to induction of anesthesia for surgery. In a Phase 1 clinical trial, 32 mg of HTX-019 as a 30-second IV injection was demonstrated to be bioequivalent to oral aprepitant 40 mg. The NDA for HTX-019 for PONV was submitted in November 2021 and the FDA set a PDUFA goal date of September 17, 2022.

About CINVANTI for Chemotherapy Induced Nausea and Vomiting (CINV) Prevention

CINVANTI, in combination with other antiemetic agents, is indicated in adults for the prevention of acute and delayed nausea and vomiting associated with initial and repeat courses of highly emetogenic cancer chemotherapy (HEC) including high-dose cisplatin as a single-dose regimen, delayed nausea and vomiting associated with initial and repeat courses of moderately emetogenic cancer chemotherapy (MEC) as a single-dose regimen, and nausea and vomiting associated with initial and repeat courses of MEC as a 3-day regimen. CINVANTI is an IV formulation of aprepitant, an NK1 RA. CINVANTI is the first IV formulation to directly deliver aprepitant, the active ingredient in EMEND capsules. Aprepitant (including its prodrug, fosaprepitant) is the only single-agent NK1 RA to significantly reduce nausea and vomiting in both the acute phase (0–24 hours after chemotherapy) and the delayed phase (24–120 hours after chemotherapy). The FDA-approved dosing administration included in the U.S. prescribing information for CINVANTI include 100 mg or 130 mg administered as a 30-minute IV infusion or a 2-minute IV injection.

Please see full prescribing information at www.CINVANTI.com.

About SUSTOL for CINV Prevention

SUSTOL is indicated in combination with other antiemetics in adults for the prevention of acute and delayed nausea and vomiting associated with initial and repeat courses of moderately emetogenic chemotherapy (MEC) or anthracycline and cyclophosphamide (AC) combination chemotherapy regimens. SUSTOL is an extended-release, injectable 5-hydroxytryptamine type 3 RA that utilizes Heron’s Biochronomer drug delivery technology to maintain therapeutic levels of granisetron for ≥5 days. The SUSTOL global Phase 3 development program was comprised of two, large, guideline-based clinical studies that evaluated SUSTOL’s efficacy and safety in more than 2,000 patients with cancer. SUSTOL’s efficacy in preventing nausea and vomiting was evaluated in both the acute phase (0–24 hours after chemotherapy) and delayed phase (24–120 hours after chemotherapy).

On May 9, 2022 bluebird bio, Inc. (NASDAQ: BLUE) ("bluebird bio" or the "Company") reported financial results and business highlights for the first quarter ended March 31, 2022, and shared recent operational progress (Press release, bluebird bio, MAY 9, 2022, View Source [SID1234613918]).

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"For more than a decade, bluebird bio has helped chart the path for the field of gene therapy and today, we are closer than ever before to realizing our mission of bringing potentially curative gene therapies to patients and their families," said Andrew Obenshain, chief executive officer, bluebird bio. "We have taken action to sharpen our focus and our finances, as the FDA completes its review of the beti-cel and eli-cel BLAs, and we prepare for the launch of two gene therapies in the second half of the year. In parallel, we are actively collecting the manufacturing comparability data required for lovo-cel and remain focused on submitting our BLA for sickle cell disease to the FDA in Q1 2023."

RECENT HIGHLIGHTS

BETI-CEL AND ELI-CEL

ADVISORY COMMITTEE MEETING ON JUNE 9-10, 2022 – On April 13, the U.S Food and Drug Administration (FDA) confirmed its plans to review betibeglogene autotemcel (beti-cel) and elivaldogene autotemcel (eli-cel) in an FDA Cellular, Tissue and Gene Therapies Advisory Committee Meeting that will take place over two days on June 9-10, 2022. The advisory committee will discuss the efficacy and safety data supporting the benefit/risk of beti-cel and eli-cel respectively, as well as safety information relevant to both therapies. If approved, beti-cel and eli-cel would be the Company’s first FDA approved therapies as an independent severe genetic disease company. An overview of the agenda was included in the Federal Register announcement posted on April 13. The full agenda will be determined by the FDA and included in briefing materials that will be posted by the FDA closer to the date of the advisory committee meeting.
LOVO-CEL

CONTINUED PROGRESS TOWARD BLA SUBMISSION – bluebird bio has enrolled more than half of the patients in the HGB-210 study that will be needed to support manufacturing data requirements for the lovotibeglogene autotemcel (lovo-cel) biologics licensing application (BLA) and the Company is on track to submit a BLA to the FDA for sickle cell disease (SCD) in the first quarter of 2023. As previously communicated, the Company has treated all patients in HGB-206 Group C who will form the primary basis of efficacy for BLA submission, with the demonstration of analytical comparability and validation of the commercial manufacturing process as the key remaining actions prior to submission of the planned BLA. Enrollment and dosing for patients 18 and older are continuing in the HGB-210 study and the Company remains in active dialogue with the FDA about the resolution of the partial clinical hold for patients under 18.
COMPANY

RESTRUCTURING UPDATE – On April 5, 2022, bluebird bio announced a comprehensive restructuring intended to deliver up to $160 million in cost savings over the next two years, reduce its workforce by approximately 30% and extend its cash runway into the first half of 2023. Near-term cost savings were realized in April as bluebird began implementing the restructuring. The Company continues to evaluate additional financing options, including public or private equity financings and monetizing any priority review vouchers that may be issued upon approval of beti-cel or eli-cel.
NEW HEADQUARTERS MOVE –bluebird bio has begun transitioning to its new headquarters in Assembly Row. The Company’s new HQ is designed to reflect modern ways of working and estimated to result in more than $120 million in cost savings over the next six years. bluebird will maintain laboratory space and operations at 60 Binney St. in Cambridge through 2023.
UPCOMING INVESTOR EVENTS

Members of the management team will participate in the following upcoming investor conferences:

BofA Securities 2022 Health Care Conference, Wednesday, May 11, at 3:20 p.m. PT at the Encore Hotel, Las Vegas, NV
2022 RBC Capital Markets Global Healthcare Conference, Tuesday, May 17, at 8:00 a.m. ET at the Intercontinental NY Barclay, New York, NY
Goldman Sachs 43rd Annual Global Healthcare Conference, Wednesday, June 15, at 4:00 p.m. PT at the Terranea Resort, Rancho Palos Verdes, CA
To access the live webcast of bluebird bio’s presentations, please visit the "Events & Presentations" page within the Investors & Media section of the bluebird bio website at View Source A replay of the webcasts will be available on the bluebird bio website for 90 days following the event.

UPCOMING ANTICIPATED MILESTONES

LOVO-CEL

The Company is in active communication with the FDA to resolve the partial clinical hold and resume enrollment and treatment of patients under the age of 18.
The Company plans to complete manufacturing of commercial drug product validation lots by mid-2022.
The Company expects to confirm vector and drug product analytical comparability by Q4 2022.
The Company plans to submit its BLA for lovo-cel in Q1 2023.
BETI-CEL

The FDA has set a PDUFA goal date of August 19, 2022, for a decision on the approval of beti-cel in patients with β-thalassemia with commercial launch expected to follow in the beginning of Q4 2022 if approved.
An FDA advisory committee meeting for beti-cel and eli-cel will be held over the course of two days on June 9-10, 2022.
ELI-CEL

The FDA has set a PDUFA goal date of September 16, 2022, for a decision on the approval of eli-cel in patients with cerebral adrenoleukodystrophy with therapy availability expected in Q4 2022 if approved.
An FDA advisory committee meeting for beti-cel and eli-cel will be held over the course of two days on June 9-10, 2022.
bluebird bio is in active communication with the FDA to resolve the clinical hold and anticipates the FDA’s questions may be resolved concurrent with the agency’s ongoing review of the Company’s BLA submission.
FIRST QUARTER 2022 FINANCIAL RESULTS

Cash Position: The Company’s restricted cash, cash and cash equivalents and marketable securities balance was approximately $312 million, including restricted cash of approximately $45 million, as of March 31, 2022. The full-year 2022 cash burn is expected to be less than $340 million with a 35 to 40 percent reduction in operating costs anticipated by year-end 2022.

The Company is exploring multiple financing opportunities, including public or private equity financings and monetizing any priority review vouchers that may be issued upon approval of beti-cel or eli-cel.
Revenues: Total revenue was $1.9 million for the three months ended March 31, 2022, compared to $0.9 million for the three months ended March 31, 2021.
R&D Expenses: Research and development expenses from continuing operations were $77.9 million for the three months ended March 31, 2022, compared to $82.8 million for the three months ended March 31, 2021. The decrease of $4.9 million was primarily due to decreased employee compensation, benefit, and other head-count related expenses, offset by increased manufacturing costs.
SG&A Expenses: Selling, general and administrative expenses from continuing operations were $36.1 million for the three months ended March 31, 2022, compared to $63.6 million for the three months ended March 31, 2021. The decrease of $27.5 million was primarily due to decreased employee compensation, benefit, and other head-count related expenses and decreased commercial readiness activities due to the Company’s decision to focus its efforts on the U.S. market for beti-cel, eli-cel, and lovo-cel.
Net Loss: Net loss from continuing operations was $122.2 million for the three months ended March 31, 2022, compared to $121.5 million for the three months ended March 31, 2021.