On November 3, 2021 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 third quarter ended September 30, 2021 and provided a corporate update (Press release, Arvinas, NOV 3, 2021, View Source [SID1234594214]).

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"The team at Arvinas has made a number of significant achievements throughout the year, from initiating multiple clinical trials to completing a potentially transformational collaboration with Pfizer, further establishing our leadership position in the field of targeted protein degradation," said John Houston, Ph.D., chief executive officer at Arvinas. "We believe the upcoming presentation of data from the completed Phase 1 dose escalation study with ARV-471 for the treatment of patients with locally advanced or metastatic ER+/HER2- breast cancer sets us up for a strong finish to what so far has been an important year of execution."

"As we look ahead, our collaboration with Pfizer has enabled us to further evaluate the most efficient development pathway for ARV-471," continued Dr. Houston. "In addition to initiating multiple planned Phase 3 studies with ARV-471 in 2022, we now intend to initiate the Phase 1b combination study with everolimus, potentially as part of a planned umbrella study with multiple combination agents with Pfizer, as well as the neoadjuvant study, in 2022. Additionally, we expect to present the full dose escalation data from the ARV-110 Phase 1 trial and an interim readout from the ARDENT Phase 2 expansion trial at ASCO (Free ASCO Whitepaper) Genitourinary Cancers Symposium in February 2022, an opportunity to showcase a more complete picture of the potential of ARV-110 in metastatic castration-resistant prostate cancer."

Business Highlights and Recent Developments

Initiated Phase 1b combination trial with ARV-110 and abiraterone for the treatment of metastatic castration-resistant prostate cancer (mCRPC).
Completed global collaboration with Pfizer that included an upfront payment to Arvinas of $650 million, a $350 million equity investment from Pfizer, and $1.4 billion in potential milestone payments to co-develop and co-commercialize ARV-471 to the treatment of patients with ER+ breast cancer. Arvinas and Pfizer will equally share worldwide development costs, commercialization expenses, and profits.
Anticipated Milestones and Expectations

ARV-471

Present Phase 1 dose escalation trial data (San Antonio Breast Cancer Symposium, December 2021)
Present data from the VERITAC Phase 2 expansion trial (200 and 500 mg) (2022)
Present safety data from the Phase 1b combination study with palbociclib (2022)
Initiate multiple Phase 3 trials in metastatic breast cancer (as monotherapy and in combination) (2022)
Initiate Phase 1b combination trial with everolimus in 2L/3L metastatic breast cancer, potentially as part of a planned umbrella study with Pfizer to explore multiple combination agents (2022)
Initiate Phase 2 neoadjuvant trial in early breast cancer (2022)
ARV-110

Present completed Phase 1 dose escalation data at ASCO (Free ASCO Whitepaper) Genitourinary Cancers Symposium (February 2022)
Present interim data from the ARDENT Phase 2 dose expansion (420 mg) at ASCO (Free ASCO Whitepaper) Genitourinary Cancers Symposium (February 2022)
ARV-766

Announce Phase 1 dose escalation data in mCRPC (2022)
Initiate Phase 2 expansion trial in mCRPC (2022)
Third Quarter Financial Results

Cash, Cash Equivalents, Restricted Cash and Marketable Securities Position: As of September 30, 2021, cash, cash equivalents, restricted cash and marketable securities were $1,549.0 million as compared with $688.5 million as of December 31, 2020. The increase in cash, cash equivalents, restricted cash and marketable securities of $860.5 million for the first nine months of 2021 was primarily related to cash received from the global Pfizer collaboration agreement to develop and commercialize ARV-471 (ARV-471 Collaboration Agreement) of $650.0 million, the equity investment by Pfizer of $350.0 million and proceeds from the exercise of stock options of $14.7 million, partially offset by cash used in operating activities of $133.9 million (net of $4.2 million received from two collaborators), professional fees associated with the global Pfizer collaboration and equity investment of $17.5 million, and the purchase of lab equipment and leasehold improvements of $2.8 million.

Research and Development Expenses: Research and development expenses were $40.6 million for the quarter ended September 30, 2021, as compared with $30.0 million for the quarter ended September 30, 2020. The increase in research and development expenses of $10.6 million for the quarter was primarily due to an increase in our continued investment in our platform and exploratory programs of $9.0 million and an increase in expenses related to our AR program (which includes ARV-110 and ARV-766) of $3.5 million, partially offset by a decrease in our ER program of $1.9 million, which includes the cost sharing of ARV-471 under the ARV-471 Collaboration Agreement with Pfizer.

General and Administrative Expenses: General and administrative expenses were $16.0 million for the quarter ended September 30, 2021, as compared with $9.3 million for the quarter ended September 30, 2020. The increase of $6.7 million was primarily due to an increase in personnel and facility related costs of $5.0 million and insurance and professional fees of $1.7 million.

Revenues: Revenues were $9.3 million for the quarter ended September 30, 2021 as compared to $7.6 million for the quarter ended September 30, 2020. Revenue is related to the ARV-471 Collaboration Agreement with Pfizer that was initiated in July 2021, 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 $1.7 million was primarily due to revenue from the ARV-471 Collaboration Agreement with Pfizer, partially offset by the addition of new targets added in 2020 under the January 2018 Pfizer Collaboration Agreement extending the revenue recognition period.

Net Loss: Net loss was $46.8 million for the quarter ended September 30, 2021, as compared with $30.8 million for the quarter ended September 30, 2020. The increase in net loss for the quarter was primarily due to increased research and development expenses and increased general and administrative expenses, partially offset by increased revenue.

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

ARV-110 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.

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 November 3, 2021 Heron Therapeutics, Inc. (Nasdaq: HRTX), a commercial-stage biotechnology company focused on improving the lives of patients by developing best-in-class treatments to address some of the most important unmet patient needs, reported financial results for the three and nine months ended September 30, 2021 and highlighted recent corporate updates (Press release, Heron Therapeutics, NOV 3, 2021, View Source [SID1234594213]).

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Recent Corporate Updates

Acute Care Franchise

ZYNRELEF Now Available:
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. ZYNRELEF became commercially available in the U.S. on July 1, 2021, and net product sales for the three and nine months ended September 30, 2021 were $2.1 million.
During the first quarter of commercial launch, 160 unique accounts purchased ZYNRELEF with 50% of those accounts reordering the product.
As of October 31, 2021, ZYNRELEF has received 126 formulary approvals, representing over a 91% hospital approval rate, and an additional 150 formulary review meetings are scheduled before the end of 2021.
Multiple commercial and Medicaid payers covering over 88 million lives have agreed to reimburse ZYNRELEF outside of the surgical bundle payment for surgeries performed in ambulatory surgical centers (ASC), with many of these covered lives also having their hospital outpatient procedures reimbursed outside the surgical bundle payment. Commercial and Medicaid payers represent >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. Medicare is currently reimbursing ZYNRELEF in outpatient settings of care under a miscellaneous C-code at 95% of the Average Wholesale Price until December 31, 2021.
Heron announced on October 4, 2021, the filing of a supplemental NDA (sNDA) for expansion of the ZYNRELEF indication statement based on the outcome of a Type C meeting with the FDA. At this meeting, Heron aligned with the FDA on the content of this sNDA to support the proposed revised indication statement to include foot and ankle, small–to–medium open abdominal, and lower extremity total joint arthroplasty surgical procedures.
At the Type C meeting, Heron also aligned with the FDA on the data needed to support a future sNDA to further expand the ZYNRELEF indication statement to broadly include soft tissue and orthopedic surgical procedures with pharmacodynamic, pharmacokinetic and safety data from a limited number of additional procedures. The studies in these additional surgeries are already in progress with the plan to submit the next sNDA in the second half of 2022.
Heron recently received FDA approval in less than 4 months of a manufacturing supplement to the NDA for ZYNRELEF to add a large-scale secondary supplier of our proprietary polymer, which will allow for the manufacturing of millions of doses of ZYNRELEF annually at a significantly reduced cost of products sales.
NDA for HTX-019 for Prevention of PONV in Adults Planned in Late 2021: A 505(b)(2) NDA for HTX-019 is planned for the prevention of postoperative nausea and vomiting (PONV) in adults. A Pre-NDA meeting with the FDA was held in August 2021 and the NDA is on track for filing in the fourth quarter of this year.
Oncology Care Franchise

2021 Oncology Care Franchise Net Product Sales: For the three and nine months ended September 30, 2021, oncology care franchise net product sales were $21.1 million and $63.6 million, respectively, compared to $20.0 million and $68.0 million, respectively, for the same periods in 2020. During 2021, Heron’s oncology care franchise net product sales have stabilized. Key factors influencing our results are the lower rate of new cancer patient treatment starts due to the continued impact of the COVID-19 pandemic, resulting in fewer clinic anti-emetic administrations during the first nine months of 2021 compared to the prior year, and the impact of value-based payer reimbursement.
CINVANTI Net Product Sales: Net product sales of CINVANTI (aprepitant) injectable emulsion for the three and nine months ended September 30, 2021 were $18.0 million and $56.2 million, respectively, compared to $19.8 million and $67.6 million, respectively, for the same periods in 2020.
SUSTOL Net Product Sales: Net product sales of SUSTOL (granisetron) extended-release injection for the three and nine months ended September 30, 2021 were $3.1 million and $7.4 million, respectively, compared to $0.2 million and $0.4 million, respectively, for the same periods in 2020.
2021 Oncology Care Franchise Net Product Sales Guidance: Heron currently expects fourth quarter of 2021 net product sales for the oncology care franchise in the range of $20 million to $22 million.
"The approval and commercial launch of ZYNRELEF, the first and only FDA-approved extended-release dual-acting local anesthetic, is an important advancement in the field of pain management. Laying the groundwork for long-term growth, we have had excellent success with the pharmacy and therapeutics committee approvals in our first quarter of launch and the number of accounts already ordering the product. With agreement from the FDA, we have submitted the first of our planned sNDAs designed to expand the ZYNRELEF label, which we believe will substantially expand the commercial opportunity for ZYNRELEF," said Barry Quart, Pharm.D., Chairman and Chief Executive Officer of Heron. "For our oncology care franchise, we have stabilized sales in a market dominated by generics and expect to see moderate growth in net product sales in 2022. Overall, we have reduced the net cash used for operating activities by 15% compared to the prior quarter and we expect to continue to further reduce it by more than 10% next quarter."

Financial Results

Net product sales for the three and nine months ended September 30, 2021 were $23.2 million and $65.7 million, respectively, compared to $20.0 million and $68.0 million, respectively, for the same periods in 2020.

Heron’s net loss for the three and nine months ended September 30, 2021 was $52.4 million and $166.0 million, or $0.51 per share and $1.71 per share, respectively, compared to $58.2 million and $165.0 million, or $0.64 per share and $1.82 per share, respectively, for the same periods in 2020. Net loss for the three and nine months ended September 30, 2021 included non-cash, stock-based compensation expense of $11.2 million and $34.0 million, respectively, compared to $11.1 million and $34.2 million, respectively, for the same periods in 2020.

As of September 30, 2021, Heron had cash, cash equivalents and short-term investments of $202.8 million, compared to $208.5 million as of December 31, 2020. Net cash used for operating activities for the nine months ended September 30, 2021 was $158.1 million, compared to $132.3 million for the same period in 2020. The increase in our net cash used for operating activities was primarily due to changes in working capital related to the launch of ZYNRELEF in July 2021, including manufacturing of commercial inventory. We expect net cash used for operating activities of $45 million to $48 million in the fourth quarter of 2021, and we anticipate that our net cash usage will continue to moderate lower in 2022 as net product sales increase and we realize cost savings from anticipated larger-scale manufacturing.

Conference Call and Webcast

Heron will host a conference call and webcast on November 3, 2021 at 4:15 p.m. ET. The conference call can be accessed by dialing 877-311-5906 for domestic callers and 281-241-6150 for international callers. Please provide the operator with the passcode 7242566 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 modified-release local anesthetic to be classified by the FDA as an "extended-release" product because ZYNRELEF is also 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 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. Safety and efficacy have not been established in highly vascular surgeries, such as intrathoracic, large multilevel spinal, and head and neck procedures. At a Type C meeting with the FDA, following the ZYNRELEF NDA approval, we aligned with the FDA on the content of an sNDA for proposed expansion of the ZYNRELEF indication statement to include foot and ankle, small–to–medium open abdominal, and lower extremity total joint arthroplasty surgical procedures without the need for additional clinical studies. The sNDA is based on the consistent safety, efficacy and pharmacokinetic data from previously completed clinical trials and was submitted to the FDA in late September 2021. 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.

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, 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. A successful Pre-NDA meeting with the FDA was held in August 2021 and the NDA is on track for filing in the fourth quarter of this year.

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 is 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).

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

On November 3, 2021 CRISPR Therapeutics (Nasdaq: CRSP), a biopharmaceutical company focused on creating transformative gene-based medicines for serious diseases, reported financial results for the third quarter ended September 30, 2021 (Press release, CRISPR Therapeutics, NOV 3, 2021, View Source [SID1234594212]).

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"The third quarter marked significant progress across our portfolio," said Samarth Kulkarni, Ph.D., Chief Executive Officer of CRISPR Therapeutics. "With our partner Vertex, we achieved target enrollment for the CTX001 clinical trials in patients with beta thalassemia and sickle cell disease, which can support regulatory submissions in late 2022. Additionally, we demonstrated proof of concept for our allogeneic CAR-T platform with positive data from our CARBON trial of CTX110, which showed that immediately available "off-the-shelf" cell therapies can offer efficacy similar to autologous CAR-T with a differentiated safety profile for patients with large B-cell lymphomas. Based on these encouraging results, we plan to expand the CARBON trial into a potentially registrational trial in the first quarter of 2022. Furthermore, we hope to bring these transformative allogeneic CAR-T therapies to patients in outpatient and community oncology settings, enabling broad access."

Recent Highlights and Outlook

Beta Thalassemia and Sickle Cell Disease

Data presented to date for 22 patients with greater than 3 months of follow-up support the profile of CTX001 as a one-time functional cure for patients with TDT and severe SCD, showing consistent and durable benefit across all treated patients.
Target enrollment has been achieved in the ongoing clinical trials for CTX001 in TDT and SCD, with planned regulatory submissions in late 2022.
Immuno-Oncology

On October 12, 2021, CRISPR Therapeutics announced positive results from its ongoing Phase 1 CARBON trial evaluating the safety and efficacy of CTX110, its wholly-owned allogeneic chimeric antigen receptor T cell (CAR-T) investigational therapy targeting CD19+ B-cell malignancies. The data showed early evidence of a dose dependent response to CTX110, with overall response rates (ORR), complete response rates (CR) and durability similar to approved autologous CD19 CAR-T therapies on an intent-to-treat (ITT) basis. A single dose of CTX110 at DL2 and above resulted in a 58% ORR and 38% CR rate in large B-cell lymphoma (LBCL) patients on an ITT basis. The pharmacokinetic data provide a strong rationale that consolidation dosing can improve on an already competitive profile for CTX110. Based on the safety and efficacy profile, the Company plans to expand into a potential registrational trial that incorporates consolidation dosing in Q1 2022.
In addition to CTX110, CRISPR Therapeutics has ongoing Phase 1 clinical trials assessing safety and efficacy of several dose levels for the following CAR-Ts: (i) CTX120, its wholly-owned allogeneic CAR-T investigational therapy targeting B-cell maturation antigen for the treatment of relapsed or refractory multiple myeloma; and (ii) CTX130, its wholly-owned allogeneic CAR-T investigational therapy targeting CD70 for the treatment of both solid tumors and certain hematologic malignancies. Based on the learnings from CTX110, the Company is implementing consolidation dosing protocols for its CTX120 and CTX130 clinical trials and expects to report top-line data in the first half of 2022.
In October, CRISPR Therapeutics announced two poster presentations at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) 36th Annual Meeting, to be held both virtually and at the Walter E. Washington Convention Center in Washington, D.C., from November 10 to 14, 2021. The Company also announced an oral presentation at the SITC (Free SITC Whitepaper) 2021 Pre-Conference Program, The Evolution of Immunotherapy: An Exploration of Immunity Beyond T cells, CAR T in Solid Tumors and Novel Combinations, which will be held from 2:00 p.m. – 6:00 p.m. ET on November 10, 2021.

Regenerative Medicine and In Vivo Programs:

CRISPR Therapeutics and its partner ViaCyte remain on track to initiate a Phase 1/2 trial of their allogeneic stem cell-derived therapy for the treatment of Type 1 diabetes in 2021. The combination of ViaCyte’s stem cell capabilities and CRISPR Therapeutics’ gene editing capabilities has the potential to enable a beta-cell replacement product that may deliver durable benefit to patients without requiring immune suppression.
The Company continues to make progress with its in vivo approaches for liver gene editing. The Company expects to move multiple programs utilizing in vivo approaches into the clinic in the next 18 to 24 months.
Other Corporate Matters

In October, CRISPR Therapeutics announced the appointment of Brendan Smith as Chief Financial Officer. Mr. Smith brings more than 20 years of financial, operational and strategic leadership experience, most recently as the Chief Financial Officer of Translate Bio.
Third Quarter 2021 Financial Results

Cash Position: Cash, cash equivalents and marketable securities were $2,477.4 million as of September 30, 2021, compared to $2,589.4 million as of June 30, 2021. The decrease in cash of $112.0 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 $0.3 million for the third quarter of 2021, compared to $0.1 million for the third quarter of 2020. Collaboration revenue primarily consisted of revenue recognized in connection with our collaboration agreements with Vertex.

R&D Expenses: R&D expenses were $105.3 million for the third quarter of 2021, compared to $71.0 million for the third quarter of 2020. The increase in expense was driven by development activities supporting the advancement of the hemoglobinopathies program and wholly-owned immuno-oncology programs, as well as increased headcount and supporting facilities related expenses.

G&A Expenses: General and administrative expenses were $24.4 million for the third quarter of 2021, compared to $21.5 million for the third quarter of 2020. The increase in general and administrative expenses for the year was primarily driven by headcount-related expense.

Net Loss: Net loss was $127.2 million for the third quarter of 2021, compared to a net loss of $92.4 million for the third quarter of 2020.

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.

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.

On November 3, 2021 Supernus Pharmaceuticals, Inc. (Nasdaq: SUPN), a biopharmaceutical company focused on developing and commercializing products for the treatment of central nervous system (CNS) diseases, reported financial results for the third quarter of 2021, and associated Company developments (Press release, Supernus, NOV 3, 2021, View Source [SID1234594211]).

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Net Product Sales

For the first nine months of 2021, net product sales were $412.5 million, a 12% increase over $368.6 million in the same period in 2020. The increase was primarily due to the acquisition of the CNS portfolio of US WorldMeds in June 2020.

Third quarter 2021 net product sales were $145.5 million, compared to $152.1 million in the same period in 2020. The decrease was primarily due to a decrease in net product sales of APOKYN and Trokendi XR, partially offset by an increase in net product sales from other products, including Qelbree, which was launched in the second quarter of 2021.

Qelbree Launch Update

Qelbree’s growth has accelerated with the arrival of the "back to school" season in the third quarter of 2021, reaching total monthly prescriptions in September of 7,132, an increase of 37% compared to August, and an increase of 118% compared to monthly average during the three months period prior to September. The latest weekly prescriptions data shows 2,248 prescriptions, an increase of 51% compared to the weekly average over the prior 12-week period.
In addition, Qelbree’s base of prescribers has increased by 340% during the third quarter of 2021 compared to the second quarter of 2021, with more than 3,470 physicians prescribing the product.
Proposed Acquisition of Adamas Pharmaceuticals, Inc. (Adamas)

On October 11, 2021, the Company announced it entered into a definitive agreement to acquire Adamas, strengthening its Parkinson’s disease portfolio with two marketed products, including GOCOVRI (amantadine) extended release capsules, the first and only FDA-approved medicine indicated for the treatment of both "off" episodes and dyskinesia in patients with Parkinson’s disease receiving levodopa-based therapy. The acquisition, if completed, would strengthen Supernus’ Parkinson’s disease portfolio with GOCOVRI and diversify and increase its revenue base and cash flow.
Per the agreement, Supernus has offered to acquire all of Adamas’ common stock through a tender offer for $8.10 per share in cash (or an aggregate of approximately $400 million) payable at closing, plus two non-transferrable and non-tradable contingent value rights collectively worth up to $1.00 per share in cash (or an aggregate of approximately $50 million), for a total consideration of up to $9.10 per share in cash (or an aggregate of approximately $450 million). The transaction is subject to customary closing conditions and is expected to close in late fourth quarter 2021 or in early first quarter 2022.
Product Pipeline Update

Qelbree (viloxazine, extended-release capsules) – Novel non-stimulant for the treatment of ADHD in adults

The U.S. Food and Drug Administration (FDA) acknowledged it has received the supplemental new drug application (sNDA) for Qelbree for the treatment of ADHD in adult patients. The sNDA has a user fee goal date (PDUFA date) of April 29, 2022.
SPN-830 (apomorphine infusion pump) – Continuous treatment of motor fluctuations ("on-off" episodes) in Parkinson’s disease (PD)

The Company expects to resubmit the SPN-830 NDA to the FDA in November 2021.
SPN-820 – Novel first-in-class activator of mTORC1

An Investigational New Drug (IND) application was submitted to the FDA in September 2021. Consequently, the randomized Phase II clinical study of SPN-820 in treatment-resistant depression is on track and expected to start by the end of 2021.
SPN-817 – A novel product candidate for the treatment of epilepsy

A randomized Phase II clinical study of SPN-817 for the treatment of focal seizures is expected to start in the second half of 2022.
SPN-443 and SPN-446 – Two novel CNS drug candidates nominated for development

The Company’s internal research and development discovery program generated several new chemical entities (NCEs) including SPN-443 and SPN-446 that were nominated for development for various CNS indications including ADHD.
Financial Highlights

For the three months ended September 30, 2021, operating earnings, net earnings and diluted earnings per share were $32.6 million, $21.6 million and $0.40, respectively, as compared to $56.1 million, $40.0 million and $0.74, for the same period in 2020.

For the nine months ended September 30, 2021, operating earnings, net earnings and diluted earnings per share were $79.9 million, $51.0 million and $0.94, respectively, as compared to $130.7 million, $96.2 million and $1.79, for the same period in 2020.

Amortization of intangible assets expense for the three and nine months ended September 30, 2021 was $6.0 million and $18.0 million, respectively, compared to $6.1 million and $9.8 million, for the same periods in 2020.

As of September 30, 2021, the Company had $849.3 million in cash, cash equivalents, current and long-term marketable securities, compared to $772.9 million as of December 31, 2020.

Full Year 2021 Financial Guidance

For full year 2021, the Company increases its financial guidance for operating earnings, lowers its financial guidance for total combined R&D and SG&A expenses, and lowers the top end of its financial guidance range for total revenues as set forth below:

(2) Operating earnings include amortization of intangible assets and contingent consideration expense (gain).
(3) The full year 2021 effective tax rate guidance of 28% – 31% is above the normally expected range of 26% – 28% primarily due to the effect of a one-time tax item in the period.

Conference Call Details

Supernus will host a conference call and webcast today, November 3, 2021, at 4:30 p.m. Eastern Time to discuss these results.

Please refer to the information below for conference call dial-in information and webcast registration. Callers should dial in approximately 10 minutes prior to the start of the call.

Following the live call, a replay will be available on the Company’s website, www.supernus.com, under "Investor Relations".

On November 3, 2021 Navidea Biopharmaceuticals, Inc. (NYSE American: NAVB) ("Navidea" or the "Company"), a company focused on the development of precision immunodiagnostic agents and immunotherapeutics, reported it will host a conference call and webcast on Wednesday, November 10, 2021 at 5:00 p.m. (EST) to discuss financial results and corporate developments for the third quarter ended September 30, 2021 (Press release, Navidea Biopharmaceuticals, NOV 3, 2021, View Source [SID1234594210]).

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Dr. Michael Rosol, Chief Medical Officer, and Erika Eves, Vice President of Finance and Administration, will host the call and webcast to discuss the financial results and provide an update on recent developments and clinical progress.

Questions will not be taken during the conference call, however you may submit questions up to 24 hours in advance of the meeting by sending an email to [email protected]. We ask that you limit your questions to those that are relevant to our business. Questions may not be addressed if they are, among other things, profane, irrelevant to our business, related to pending or threatened litigation, disorderly, or repetitious of statements already made. In addition, questions may be grouped by topic by our management with a representative question read aloud and answered. Questions will be addressed in the Q&A portion of the conference call, and we may also respond to questions on an individual basis or by posting answers on our website after the call.

To participate in the call and webcast, please refer to the information below:

A live audio webcast of the conference call will also be available on the investor relations page of Navidea’s corporate website at www.navidea.com. In addition, the recorded conference call can be replayed and will be available for 90 days following the call on Navidea’s website.