On November 1, 2023 Seagen Inc. (Nasdaq:SGEN) (Seagen or the Company) reported financial results today for the third quarter ended September 30, 2023 (Press release, Seagen, NOV 1, 2023, View Source [SID1234636657]).

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David Epstein, Chief Executive Officer of Seagen said, "Seagen continues to build momentum in 2023 and delivered strong performance, marked by record quarterly net product sales, with significant year-over-year growth of 33%, contributing to total revenues of $649 million. Growth was primarily driven by PADCEV (enfortumab vedotin-ejfv), which grew 89% over the same quarter of last year following the successful launch in the U.S. in combination with Keytruda (pembrolizumab) as a front-line treatment for patients with advanced urothelial cancer who are not eligible to receive cisplatin-containing chemotherapy. We also announced positive trial readouts across our commercial portfolio in multiple patient settings." Highlights include:

PADCEV in combination with Keytruda demonstrated a 53% reduction in the risk of death and a near doubling in the median overall survival (OS) (31.5 months vs 16.1 months) versus chemotherapy in patients with previously untreated locally advanced or metastatic urothelial cancer (la/mUC) who were eligible for cisplatin- or carboplatin-containing chemotherapy regardless of PD-L1 status. Data from the global phase 3 study, EV-302 / KEYNOTE-A39, were presented during the Presidential Symposium at the European Society of Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress in October.
TIVDAK (tisotumab vedotin-tftv) demonstrated superior overall survival with a 30% reduction in the risk of death in the innovaTV 301 pivotal trial for patients with recurrent or metastatic cervical cancer with disease progression on or after first-line therapy. Additionally, progression-free survival was statistically significant with a 33% reduction in the risk of disease worsening or death compared with chemotherapy and the confirmed objective response rate was also improved with TIVDAK (17.8%) compared with chemotherapy (5.2%). Results were presented during the Presidential Symposium at ESMO (Free ESMO Whitepaper).
The HER2CLIMB-02 pivotal trial of TUKYSA (tucatinib) in combination with antibody-drug conjugate (ADC) ado-trastuzumab emtansine met the primary endpoint of progression-free survival in patients with previously treated HER2-positive metastatic breast cancer.
"We remain very excited about the pending acquisition of Seagen by Pfizer as we look to build a world-class oncology organization which will broaden patient reach and accelerate development of our innovative pipeline," concluded Mr. Epstein.

Roger Dansey, President of Research and Development and Chief Medical Officer, added, "We have now demonstrated an overall survival benefit in targeted indications across all four of our approved products. The PADCEV EV-302 study has the potential to be practice changing and offer a new standard of care for first-line metastatic bladder cancer. Building on our expertise and innovative platform, we are advancing next-generation ADC and immuno-oncology targeted therapies. We recently initiated a phase 3 trial of disitamab vedotin in combination with pembrolizumab in patients with previously untreated locally advanced or metastatic HER2-positive urothelial cancer, along with a phase 1 trial for SGN-EGFRd2, a novel T cell engaging bispecific antibody. We also remain on track to initiate a phase 3 trial of SGN-B6A in patients with previously treated non-small cell lung cancer and to meet our goal of submitting four Investigational New Drug (IND) applications for novel drug candidates in 2023 before year end."

PRODUCTS HIGHLIGHTS

PADCEV

Positive Results for the Phase 3 EV-302 Trial of the Combination of PADCEV and Keytruda as First-Line Treatment for Advanced Urothelial Cancer Presented at the ESMO (Free ESMO Whitepaper) Congress: In October 2023,data from the phase 3 EV-302 trial, which was conducted in collaboration with Merck and our partner Astellas, were presented during the Presidential Symposium at ESMO (Free ESMO Whitepaper) in a late-breaking oral presentation demonstrating a 53% reduction in risk of death with PADCEV and Keytruda compared to chemotherapy in patients with previously untreated locally advanced or metastatic urothelial cancer (la/mUC). The combination improved median overall survival by more than 15 months versus chemotherapy. OS results were consistent across all pre-defined subgroups, including cisplatin eligibility and PD-L1 expression level. The safety results in EV-302 were consistent with those previously reported with this combination in EV-103 in cisplatin-ineligible patients with la/mUC. No new safety signals were identified. An extension study in China continues to enroll patients. The EV-302 trial is intended to serve as the basis for global submissions and as the confirmatory trial for the U.S. accelerated approval of this combination. We intend to submit a supplemental Biologics License Application (sBLA) to the U.S. Food and Drug Administration (FDA) this year.
Data Presented for Muscle-Invasive Bladder Cancer (MIBC) at ESMO (Free ESMO Whitepaper): In October 2023, data from Cohort L of the EV-103 phase 1b/2 trial evaluating PADCEV monotherapy as perioperative treatment in cisplatin-ineligible patients with MIBC were presented demonstrating promising activity and a generally manageable safety profile.
ADCETRIS

European Commission Approves ADCETRIS in Combination with Chemotherapy in Previously Untreated CD30+ Stage III Hodgkin Lymphoma: In October 2023, the European Commission approved the ADCETRIS (brentuximab vedotin) combination based on updated positive overall survival results from the Phase 3 ECHELON-1 study. ADCETRIS has been previously approved as a therapy for adult patients in Europe in six distinct indications, including those with previously untreated CD30+ Stage IV Hodgkin lymphoma.
Presenting Combination Data in Metastatic Solid Tumors at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) Annual Meeting: Initial data of ADCETRIS in combination with Keytruda in metastatic solid tumors will be presented at the SITC (Free SITC Whitepaper) Annual Meeting being held November 3-5, 2023.
TUKYSA

Phase 3 HER2CLIMB-02 Trial Combining TUKYSA and Kadcyla Meets Primary Endpoint of Progression-Free Survival: In August 2023, the Company announced that the phase 3 HER2CLIMB-02 clinical trial of TUKYSA in combination with the antibody-drug conjugate Kadcyla (ado-trastuzumab emtansine) met its primary endpoint of progression-free survival (PFS), including for patients with active brain metastases. Patients in the trial had unresectable locally advanced or metastatic HER2-positive breast cancer and had received previous treatment with a taxane and trastuzumab.​ Overall survival data, a secondary endpoint, are not yet mature. Discontinuations due to adverse events were more common in the combination arm of the trial, but no new safety signals emerged for the combination. Results will be presented at an upcoming meeting.
TIVDAK

Positive Results for Phase 3 innovaTV 301 Clinical Trial Presented at ESMO (Free ESMO Whitepaper): In October 2023, data from the innovaTV 301 trial, conducted in collaboration with our partner Genmab, were presented in an oral session during the Presidential Symposium at ESMO (Free ESMO Whitepaper) that demonstrated a 30% reduction in risk of death compared to chemotherapy and a manageable and tolerable safety profile consistent with the known safety profile as presented in the U.S. prescribing information. No new safety signals were observed. The results from innovaTV 301 are intended to serve as the confirmatory trial for the U.S. accelerated approval and support potential global regulatory applications.
PIPELINE PROGRAMS

Initiated a Phase 3 Trial for Disitamab Vedotin for Patients with HER2-Positive, Metastatic Urothelial Cancer: The Company initiated a phase 3 trial evaluating disitamab vedotin in combination with pembrolizumab versus chemotherapy in patients with previously untreated locally advanced or metastatic HER2-positive urothelial cancer in the third quarter of 2023.
Planning to Initiate Phase 3 Trial for SGN-B6A in Patients with Previously Treated Non-Small Cell Lung Cancer (NSCLC) Before Year End: The Company expects to initiate a phase 3 trial for SGN-B6A, a novel, vedotin ADC targeting integrin beta-6, as a monotherapy in previously treated patients with NSCLC before the end of 2023.
Reported Initial Results for SGN-B7H4V at ESMO (Free ESMO Whitepaper): In October 2023, initial first-in-human clinical data for SGN-B7H4V were presented at ESMO (Free ESMO Whitepaper) demonstrating antitumor activity across a variety of dose levels, dose schedules and tumor types with commonly observed adverse events including peripheral neuropathy, neutropenia, diarrhea, and nausea, consistent with other ADCs. Development remains ongoing in phase 1 dose expansion cohorts in breast, endometrial, ovarian and other B7H4-expressing solid tumors.
Initiated Clinical Trial for Novel Targeted Therapy and Unveiled Novel ADC Program at AACR (Free AACR Whitepaper)-NCI-EORTC Conference: The Company initiated a phase 1 trial for SGN-EGFRd2, a gamma delta bispecific T-cell engager for EGFR-expressing solid tumors. Year to date, the Company has submitted INDs for three novel targeted cancer therapies, including SGN-EGFRd2, SGN-35T and SGN-CEACAM5C, with the goal of submitting one additional IND before year end. Preclinical data for SGN-35T, a next generation CD30-directed ADC with a novel tripeptide drug linker designed to improve the tolerability profile compared with ADCETRIS, were presented at the annual AACR (Free AACR Whitepaper)-NCI-EORTC AACR-NCI-EORTC (Free AACR-NCI-EORTC Whitepaper) International Conference on Molecular Targets and Cancer Therapeutics (EORTC-NCI-AACR) (Free ASGCT Whitepaper) (Free EORTC-NCI-AACR Whitepaper) in October.
For additional information on Seagen’s pipeline, visit www.seagen.com/science/pipeline.

CORPORATE HIGHLIGHTS

Update on Pfizer Acquisition: The European Commission approved the acquisition of Seagen by Pfizer unconditionally pursuant to Article 6(1)b under the EU Merger Regulation on October 19, 2023. The completion of the transaction remains subject to other customary closing conditions, including the expiration or termination of the waiting period under the Hart-Scott-Rodino Antitrust Improvements Act of 1976, as amended, relating to the consummation of the transaction, and the satisfaction or waiver of the other closing conditions specified in the Merger Agreement. The Company continues to expect that the transaction will be completed in late 2023 or early 2024.
Annual Corporate Responsibility Report Published, Detailing ESG Commitments: Seagen continues to push the boundaries of innovation while upholding its commitment to sustainable practices, as highlighted in the Company’s latest corporate responsibility report, Linking Breakthroughs to Lives. Accomplishments detailed include multiple positive clinical trial results and label expansions across our commercial portfolio, new DEI strategy, publishing our Human Rights Policy and Supplier Code of Conduct, enhancing governance programs across numerous areas including compliance and information security, and new environmental initiatives. Seagen is proud to announce that Newsweek named the Company one of America’s Greenest Companies 2024 and awarded it the highest rating of 5 stars, based on its ESG achievements. The report is available on Seagen’s website at View Source
THIRD QUARTER AND NINE-MONTHS 2023 FINANCIAL RESULTS

Revenues: Total revenues for the third quarter and nine months ended September 30, 2023 were $649 million and $1,772 million, respectively, compared to $510 million and $1,434 million for the same periods in 2022, primarily driven by growth in net product sales.

Revenues included the following components:

Three months ended September 30,

Nine months ended September 30,

(dollars in millions)

2023

2022

% Change

2023

2022

% Change

Total Net Product Sales

$

571

$

428

33

%

$

1,583

$

1,243

27

%

ADCETRIS

$

246

$

219

13

%

$

751

$

601

25

%

PADCEV

$

200

$

105

89

%

$

479

$

329

46

%

TUKYSA

$

102

$

88

16

%

$

289

$

267

8

%

TIVDAK

$

23

$

16

40

%

$

64

$

45

42

%

Royalty Revenues

$

64

$

44

45

%

$

145

$

111

30

%

Collaboration and License
Agreement Revenues

$

14

$

38

(63

)%

$

44

$

80

(45

)%

Note: Sum of product sales may not equal total net product sales due to rounding. Percent change reflects actual (unrounded) values.

Net Product Sales: The increases in net product sales for the third quarter and year-to-date of 2023 compared to the same periods in 2022 were driven by continued commercial execution. ADCETRIS demonstrated year-over-year growth of 13%, primarily attributed to volume growth from greater use in frontline advanced Hodgkin lymphoma, despite recent increased competition in this setting. PADCEV growth was driven by use as first-line treatment for patients with locally advanced or metastatic urothelial cancer who are not eligible to receive cisplatin-containing chemotherapy following its approval for this indication in April 2023. Of note, PADCEV sales in the year-to-date of 2022 included $19 million in sales to another company for a clinical trial they are conducting, while no such sales were booked in the year-to-date of 2023. TUKYSA performance reflects volume growth driven by the important role it serves in the treatment of HER2-positive metastatic breast cancer as well as contributions from its colorectal cancer indication. TIVDAK growth reflects continued uptake in its current indication.
Royalty Revenues: Growth in royalty revenues were primarily driven by royalties from sales of Polivy (polatuzumab vedotin) by Roche, which is an ADC that uses Seagen technology, as well as by sales of ADCETRIS outside the U.S. and Canada by Takeda.
Collaboration and License Agreement Revenues: The decrease in collaboration and license agreement revenues for the third quarter of 2023 was primarily driven by an upfront payment in the prior period and the decrease for the year-to-date also due to a prior period milestone partially offset by collaboration revenue.
Cost of Sales: Cost of sales for the third quarter and year-to-date in 2023 were $165 million and $458 million, respectively, compared to $108 million and $302 million for the same periods in 2022. The increases reflect higher sales of our medicines and the related gross profit share amounts owed to collaboration partners, which were $103 million and $249 million in the third quarter and year-to-date in 2023, respectively, compared to $71 million and $189 million for the same periods in 2022. Cost of sales also reflects amortization of TUKYSA acquired in-process technology costs, third-party royalties owed for PADCEV and TUKYSA net product sales, and cost of products sold. The year-to-date in 2023 cost of sales included a $47 million inventory write-off related to in-process production of one of our products that did not meet a release specification that was updated in June 2023. This inventory adjustment and new release specification are not expected to impact availability of product supply required to meet current or future demand.

Research and Development (R&D) Expenses: R&D expenses for the third quarter and year-to-date in 2023 were $449 million and $1,205 million, respectively, compared to $385 million and $987 million for the same periods in 2022 reflecting continued investment in clinical development of the Company’s approved drugs and pipeline programs.

Selling, General and Administrative (SG&A) Expenses: SG&A expenses for the third quarter and year-to-date in 2023 were $266 million and $746 million, respectively, compared to $210 million and $605 million for the same periods in 2022. The increases in 2023 were driven by ongoing commercialization efforts, as well as $40 million in expenses year-to-date associated with the pending acquisition by Pfizer and other corporate activities.

Non-cash, share-based compensation expense for the nine months ended September 30, 2023 was $288 million, compared to $157 million for the same period in 2022.

Net Loss: Net loss for the third quarter of 2023 was $216 million, or $1.15 per diluted share, and net loss for the year-to-date of 2023 was $602 million, or $3.21 per diluted share.

Net loss for the third quarter of 2022 was $191 million, or $1.03 per diluted share, and net loss for the year-to-date of 2022 was $462 million, or $2.51 per diluted share.

Cash and Investments: As of September 30, 2023, Seagen had $1.2 billion in cash and investments.

CONFERENCE CALL

Given the pending acquisition of Seagen by Pfizer, Seagen is no longer providing financial guidance for 2023 and will not be hosting its quarterly conference call and does not expect to do so for future quarters. Earnings materials are available publicly on the Investor Relations page of our website at investor.seagen.com. Please direct any questions to Seagen Investor Relations at the contact information below.

On November 1, 2023 Schrödinger, Inc. (Nasdaq: SDGR), whose physics-based computational platform is transforming the way therapeutics and materials are discovered, reported financial results for the quarter ended on September 30, 2023 (Press release, Schrodinger, NOV 1, 2023, View Source [SID1234636656]).

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"Schrodinger had an excellent third quarter marked by strong revenue growth and significant pipeline progress. More of our software customers are increasing the scale of their use of our technology, and we remain very confident about the outlook for the full year," said Ramy Farid, Ph.D., chief executive officer of Schrödinger. "We initiated our Phase 1 clinical study of SGR-2921 and our Phase 1 study of SGR-1505 in healthy volunteers is nearing completion. We look forward to sharing more details about our proprietary programs later this year."

Today, Schrodinger announced that the rights to two related oncology discovery programs would revert to the company, after Bristol Myers Squibb elected not to proceed with further development of these programs for strategic reasons.

Third Quarter 2023 GAAP Financial Results
•Total revenue for the third quarter was $42.6 million compared to $37.0 million in the third quarter of 2022.
•Software revenue for the third quarter was $28.9 million compared to $24.7 million in the third quarter of 2022.
•Drug discovery revenue was $13.7 million for the third quarter compared to $12.3 million in the third quarter of 2022.
•Software gross margin was 76% for the third quarter compared to 72% in the third quarter of 2022.
•Operating expenses were $79.8 million for the third quarter compared to $63.4 million for the third quarter of 2022.
•Other expense for the third quarter was $8.7 million compared to other income of $6.5 million in the third quarter of 2022, driven by changes in the fair value of equity investments and interest income.
•Net loss for the third quarter was $62.0 million, compared to $39.9 million in the third quarter of 2022.
•At September 30, 2023, Schrödinger had cash, cash equivalents, restricted cash and marketable securities of approximately $503 million, compared to approximately $456 million at December 31, 2022.

For the three and nine months ended September 30, 2023, Schrödinger reported net losses of $62.0 million and net income of $71.4 million, respectively, compared to net losses of $39.9 million and $122 million for the three and nine months ended September 30, 2022, respectively.

For the three and nine months ended September 30, 2023, Schrödinger reported non-GAAP net losses of $50.4 million and $134.8 million, respectively, compared to non-GAAP net losses of $44.9 million and $117.0 million for the three and nine months ended September 30, 2022, respectively. See "Non-GAAP Information" below and the table at the end of this press release for a reconciliation of non-GAAP net income (loss) to GAAP net income (loss).

2023 Financial Outlook
•Schrödinger today updated its financial guidance for 2023. The company’s financial expectations for the fiscal year ending December 31, 2023 are as follows:
•Software revenue growth is expected to be in the range of 15 percent to 18 percent.
•Drug discovery revenue is expected to range from $50 million to $70 million.
•Software gross margin is expected to be similar to software gross margin for the full year 2022.
•Operating expense growth in 2023 is expected to be significantly lower than operating expense growth in 2022.
•Cash used for operating activities is now expected to be higher in 2023 than 2022, based on the mix of revenue, the timing and size of milestones and expectations for new business development activity this year.
Recent Company Highlights
Wholly-Owned Pipeline
•Schrödinger continues to advance SGR-1505, its investigational MALT1 inhibitor. The Phase 1 dose-escalation study in healthy volunteers is nearing completion, and the company expects to report data from the study in the fourth quarter of 2023. Enrollment in the Phase 1 dose-escalation study in relapsed or refractory B-cell malignancy patients is ongoing in the U.S. and EU. The U.S. Food and Drug Administration recently granted Orphan Drug Designation to SGR-1505 for potential treatment in mantle cell lymphoma.

•Today Schrödinger announced the initiation of the Phase 1 clinical study of SGR-2921, an investigational CDC7 inhibitor, in patients with acute myeloid leukemia or myelodysplastic syndrome. The study is designed to evaluate the safety, pharmacokinetics, pharmacodynamics, and determine the recommended dose. SGR-2921 has exhibited anti-tumor activity as a monotherapy and in combination with standard of care agents in multiple preclinical tumor models.

•Schrödinger continues to advance SGR-3515, an inhibitor of Wee1 and Myt1. Concurrent loss of function of Wee1 and Myt1 confers selective vulnerability in cancer cells, a mechanism referred to as synthetic lethality. IND-enabling activities are ongoing to support an IND submission for SGR-3515 in the first half of 2024.

•Today Schrödinger announced that one of its previously undisclosed discovery programs is PRMT5-MTA (protein arginine methyltransferase 5/methylthioadenosine). PRMT5 has been shown to be a synthetic lethal target for MTAP-deleted cancers with potential roles in the treatment of both hematologic and solid tumors. The company expects to provide more details about its PRMT5-MTA program and other early-stage programs at its Pipeline Day on December 14, 2023.

Schrödinger Collaborators
•In October, Schrödinger collaborator Morphic Holdings presented additional Phase 2a data from the EMERALD-1 trial of MORF-057, an oral ɑ4ꞵ7 inhibitor in development for ulcerative colitis and Crohn’s disease at United European Gastroenterology (UEG) week.

•In September, Structure Therapeutics presented positive results from the Phase Ib multiple ascending dose study of GSBR-1290, an oral GLP-1R, in healthy overweight or obese individuals.

•In September, Schrödinger and the Bill & Melinda Gates Foundation renewed their agreement to invest in the discovery and development of novel non-hormonal contraceptive agents for global health.

Platform

•During the third quarter, Schrödinger and Gates Ventures LLC extended their agreement to develop and apply simulation methods to improve battery performance for a second three-year period. The new research agreement includes total consideration of $6M and runs through August 2026.

•Schrödinger announced quarterly software release 2023-3, which incorporated a number of important updates, including a major enhancement to the company’s Induced Fit Docking (IFD) technology for optimization of certain key ADMET properties, the first full release of technology that can be used to optimize antibody affinity as a function of pH, and technology to more accurately predict small molecule pKa values, a key intrinsic molecular property.

•In August, Schrödinger scientists published the results of a novel automated workflow, FEP Protocol Builder (FEP-PB), which uses active-learning to automate development of accurate FEP+ protocols, increasing the number of targets amenable to the technology.

Third Quarter 2023 Webcast and Conference Call Information
Schrödinger will host a conference call to discuss its third quarter 2023 financial results on Wednesday, November 1, 2023, at 4:30 p.m. ET. The live webcast can be accessed under "News & Events" in the investors section of Schrödinger’s website, View Source The archived webcast will be available on Schrödinger’s website for approximately 90 days following the event.

Schrödinger Pipeline Day Webcast Information
Schrödinger will host its Pipeline Day in New York City on Thursday, December 14, 2023, beginning at 10:00 a.m. ET. Pipeline Day will be a hybrid event, with limited in-person attendance available to members of the investment community, and a simultaneous webcast will be available for individual investors and other interested parties who wish to join virtually. The live presentation can be accessed in the "Investors" section of Schrödinger’s website and will be archived for approximately 90 days. To participate in the live webcast, please register for the event here. It is recommended that participants register at least 15 minutes in advance of the event.

On November 1, 2023 Sangamo Therapeutics, Inc. (Nasdaq: SGMO), a genomic medicines company, reported recent business highlights, including progress on its strategic transformation and a corresponding restructuring of operations and workforce reduction, and reported third quarter 2023 financial results (Press release, Sangamo Therapeutics, NOV 1, 2023, View Source [SID1234636655]).

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"In 2020, we shared our refreshed company strategy which aims to both maximize the potential of our proprietary genomic editing and delivery technology, and to focus on areas where we believe we can apply that technology to be either first-in-class or best-in-class. The process of streamlining Sangamo’s pipeline has been accelerated within today’s challenging economic environment and we have had to make difficult decisions to defer further investments and seek collaboration partners or direct investment in both our Fabry gene therapy and CAR-Treg cell therapy programs," said Sandy Macrae, Chief Executive Officer of Sangamo. "As we work to unlock value in our clinical programs that is not currently reflected as part of Sangamo, we plan to do everything in our power to get these important assets into the hands of parties with the means to advance them towards patients. At the same time, we will continue to progress our promising epigenetic regulation programs for neurological diseases and hope to soon share a breakthrough in our capsid delivery capabilities, which we believe could open the door for many other high-value and unmet diseases to be addressed with our editing capabilities. We continue to seek ways to raise additional capital to strengthen our financial foundation."

The restructuring announced today represents a further step towards simplifying the Sangamo organization and focusing on our epigenetic regulation therapies treating neurological diseases and our novel AAV capsid delivery technologies. Sangamo is deferring new investments in its Fabry and CAR-Treg programs beyond what is currently committed and is actively seeking collaboration partners or direct investors in both. In addition, Sangamo expects to close its Brisbane, California facility in early 2024 to conserve cash resources, and will transition its headquarters to its Richmond, California facility as of January 1, 2024. As a result of this restructuring, Sangamo is reducing its US workforce by approximately 40%, or approximately 162 roles.

In connection with the restructuring, D. Mark McClung, Executive Vice President, Chief Operating Officer and Jason Fontenot, Senior Vice President, Chief Scientific Officer will be leaving the company on January 2, 2024. In the context of a streamlined and more focused organization, we are eliminating their roles. Until his departure, Mark will continue to lead our search for partners and investors in our Fabry and CAR-Treg programs. Amy Pooler, currently serving as Vice President, Neuroscience and Gregory Davis, currently serving as Vice President, Genome Engineering Design and Technology, have been appointed as Head of Research and Head of Technology, respectively, effective November 17, 2023.

The restructuring and workforce reductions, in combination with other potential cost reductions, are anticipated to reduce our non-GAAP annual operating expenses from approximately $240 million-$260 million in 2023 to approximately $115 million-$135 million in 2024, a decrease of approximately 50%. Sangamo expects to incur approximately $8 million-$10 million in one-time restructuring costs in the fourth quarter of 2023. Sangamo believes its cash, cash equivalents, and marketable securities as of September 30, 2023, in combination with the cost savings expected from the restructuring, workforce reduction and other potential cost reductions, will be sufficient to fund its planned operations into the third quarter of 2024.
Dr. Macrae continued: "I am grateful to all our employees for their commitment to Sangamo’s mission and the patients we seek to serve, and have special appreciation to all those who are leaving for their important contributions. Additionally, I would like to personally thank Mark for the wisdom, candor and leadership he has brought to Sangamo. He has been a trusted colleague and will be greatly missed. I would also like to thank Jason for his dedication, passion and leadership. He leaves a strong scientific legacy for which we will always be grateful."

Recent Business Highlights

Program Highlights

Neurology Epigenetic Regulation Programs – Progressed IND-enabling activities for Nav1.7; presented updated preclinical data at Prion 2023; presented preclinical data on zinc finger activators at the European Society of Gene and Cell Therapy (ESGCT); made significant progress in identifying new, potentially transformative AAV delivery capsids.
•Progressed IND enabling activities for the Nav1.7 program to treat chronic neuropathic pain. Continue to expect an IND submission for this program in 2024.
•Presented data from the prion disease program at the Prion 2023 Conference in October 2023, showing in animal models that Sangamo’s zinc finger repressors significantly reduce expression of the prion protein in the brain, extend lifespan and limit the formation of toxic prion aggregates.
•Presented an oral presentation at ESGCT in October 2023, showing that our zinc finger activators can be designed to restore normal gene and protein expression of SCN2A in vitro and in vivo to potentially address neurodevelopmental disorders such as autism spectrum disorder and intellectual disability.
•Presented data on Shank3 gene activation mediated by zinc finger transcriptional activators as a potential therapeutic approach for Phelan-McDermid Syndrome at ESGCT.
•Continued to advance identification and selection of engineered AAV capsids for enhanced central nervous system delivery through both intrathecal and intravenous delivery. Anticipate sharing nonhuman primate data from our capsid development efforts in early 2024.
Fabry Disease – Dosed total of 25 patients in Phase 1/2 STAAR study; all patients dosed to date continue to demonstrate sustained, elevated α-Gal A levels for up to three years for the longest treated patient; received Regenerative Medicine Advanced Therapy (RMAT) Designation from U.S. FDA; enrolled sufficient patients in the Phase 1/2 study believed to provide a preliminary assessment of safety and efficacy; deferring Phase 3 planning investments and actively seeking partners and investment.
•Dosed three additional patients in the dose expansion phase of the Phase 1/2 STAAR study evaluating isaralgagene civaparvovec, our wholly owned gene therapy product for the treatment of Fabry disease, for a total of 25 patients dosed to date, including 14 at the planned Phase 3 dose of 5×1013 vg/kg.
•All patients dosed to date continue to demonstrate sustained, elevated α-Gal A levels, with 12 patients having achieved at least one year of follow-up and the longest treated patient having achieved three years of follow-up.
•All 11 patients who were withdrawn from enzyme replacement therapy (ERT) remain off ERT, for up to 24 months for the longest withdrawn patient.
•Treated patients continue to report improvements in their quality of life, some even over and above the benefits they were experiencing on ERT.
•Received U.S. FDA RMAT designation for isaralgagene civaparvovec, which aims to expedite the review of new therapeutics that are intended to address an unmet need in patients with serious conditions. The U.S. FDA has previously granted isaralgagene civaparvovec both Orphan Drug and Fast Track Designations.
•Stopping further screening and enrollment in the Phase 1/2 STAAR study, after successfully enrolling sufficient patients believed to provide a preliminary assessment of efficacy and safety in the Phase 1/2 study.

•Expect to complete dosing of the remaining enrolled patients in the first half of 2024.
•Anticipate presenting updated Phase 1/2 clinical data at a medical meeting in early 2024.
•Deferring additional investments in Phase 3 planning until collaboration partnership or Phase 3 trial financing is secured.
CAR-Tregs – Received approval for accelerated dosing protocol for Phase 1/2 STEADFAST study from European regulatory authorities; dosed the first patient in the second dose cohort; successfully manufactured product candidate for third and new fourth dose levels; presented updated preclinical data at ESGCT; seeking a collaboration partner or direct investment in CAR-Tregs.
•Dosed the first patient in the second cohort of the Phase 1/2 STEADFAST study evaluating TX200, our wholly owned autologous CAR-Treg cell therapy treating patients receiving an HLA-A2 mismatched kidney from a living donor.
•The product candidate continues to be generally well tolerated in all four patients dosed to date.
•Received all necessary regulatory and ethics approvals for an accelerated dose escalation protocol from European regulatory authorities that could allow dosing to advance more quickly through the cohorts and which allows for a new and highest fourth dose cohort, compared to the three cohorts in the previously approved study protocol. The new, fourth cohort dose will be 18-fold higher than the first cohort starting dose.
•Completed manufacturing of the dose for the patient in the third cohort, who recently received a kidney transplant. Dosing of this fifth patient is expected in the fourth quarter of 2023, pending approval from the Safety Monitoring Committee.
•Completed manufacturing of the dose for the first patient in the fourth and highest dose cohort, who recently received a kidney transplant. Dosing of this sixth patient is expected in January 2024, pending approval from the Safety Monitoring Committee – which would accelerate dosing plans by 18 months compared to the previously approved study protocol.
•Presented preclinical data at ESGCT demonstrating the potential of autologous MOG-CAR-Tregs to provide a long-lasting treatment option for multiple sclerosis and updated animal model data demonstrating the promise of IL23R-CAR-Tregs in the potential treatment of Crohn’s disease.
•Actively seeking a potential collaboration partner or direct external investment in the CAR-Treg cell therapy programs. Expect to provide an update on these efforts in the first quarter of 2024.
•Deferring new investments until a collaboration partner or external investment is secured.
Hemophilia A (Pfizer) – dosing complete in Phase 3 AFFINE trial; pivotal data read-out expected in mid-2024; BLA and MAA submissions anticipated in second half of 2024.
•Pfizer has advised us that dosing is complete in the Phase 3 AFFINE trial of giroctocogene fitelparvovec, an investigational gene therapy we are developing with Pfizer for patients with moderately severe to severe hemophilia A.
•A pivotal readout is expected in mid-2024, with Pfizer anticipating BLA and MAA submissions in the second half of 2024 if the pivotal readout is supportive.
•Expect to present updated data with Pfizer from the Phase 1/2 ALTA study of giroctocogene fitelparvovec in an oral presentation at the 65th American Society for Hematology Annual Meeting and Exposition on December 11, 2023.

Third Quarter 2023 Financial Results

Consolidated net loss for the third quarter ended September 30, 2023 was $104.2 million, or $0.59 per share, compared to a net loss of $53.2 million, or $0.34 per share, for the same period in 2022, primarily due to a non-cash charge relating to impairment of long-lived asset of $44.8 million, which was a result of continued decline in our stock price and related market capitalization, initiation of actions to seek external financing and reprioritize certain research and development programs, and continued decline in equity values in the biotechnology industry.
Revenues
Revenues for the third quarter ended September 30, 2023 were $9.4 million, compared to $26.5 million for the same period in 2022.
The decrease of $17.1 million in revenues was primarily attributed to a decrease of $9.6 million and $9.1 million in revenue relating to our collaboration agreements with Novartis and Biogen, respectively, due to the termination of these collaboration agreements in June 2023, and a decrease of $1.4 million in revenue relating to our collaboration agreement with Kite, reflecting a reduction in collaboration activities during the quarter. These decreases were partially offset by an increase of $3.0 million in revenue relating to our other license agreements.

Total operating expenses on a GAAP basis for the third quarter ended September 30, 2023 were $115.8 million, compared to $81.3 million for the same period in 2022. GAAP operating expenses for the third quarter ended September 30, 2023 included a non-cash charge relating to impairment of long-lived asset of $44.8 million, as described above. Non-GAAP operating expenses, which exclude impairment charges and stock-based compensation expense, for the third quarter ended September 30, 2023 were $64.8 million, compared to $73.5 million for the same period in 2022.
The decrease in total operating expenses on a non-GAAP basis was primarily attributable to lower compensation and other personnel costs mainly due to lower headcount as a result of restructuring of operations and corresponding reduction in workforce announced in April 2023, and decrease in manufacturing and lab supply expenses due to deferral and reprioritization of certain research and development programs. These decreases were partially offset by higher facilities and infrastructure related costs, and higher external expenses as we advance our clinical and preclinical pipeline.
Cash, Cash Equivalents and Marketable Securities
Cash, cash equivalents and marketable securities as of September 30, 2023 were $132.1 million, compared to $307.5 million as of December 31, 2022. As of September 30, 2023, we have raised approximately $15.1 million in net proceeds under our at-the-market offering program since January 1, 2023. We believe that our available cash, cash equivalents and marketable securities as of September 30, 2023, in combination with the cost savings expected from the restructuring, workforce reduction and other potential cost reductions, will be sufficient to fund our planned operations into the third quarter of 2024.
Updated Financial Guidance for 2023
•GAAP operating expenses, including impairment of goodwill, indefinite-lived intangible assets, and long-lived assets, and stock-based compensation expense, for the full year 2023 are now estimated to be in the range of approximately $422 million to $442 million, reflecting the additional non-cash impairment charges recorded in the third quarter. The previous GAAP operating expenses guidance provided on August 8, 2023 was in the range of approximately $378 million to $398 million.
•We continue to estimate non-GAAP operating expenses to be in the range of approximately $240 million to $260 million, which remains unchanged from the last update on April 26, 2023. Estimated non-GAAP operating expenses exclude impairment of goodwill of $38.1 million, impairment of indefinite-lived intangible assets of $51.3 million, impairment of long-lived assets of $65.2 million, and stock-based compensation expense of $28.0 million.
Upcoming Events
Sangamo plans to participate in the following events:
Investor Conferences
•Truist Securities BioPharma Symposium, November 8-9, 2023
•Jefferies London Healthcare Conference, November 14-16, 2023
•EvercoreISI HealthCONx, November 28-30, 2023
Access links for available webcasts for these investor conferences will be available on the Sangamo website in the Investors and Media section under Events. Available materials will be found on the Sangamo website after the event under Presentations.

Conference Call to Discuss Third Quarter 2023 Results

The Sangamo management team will discuss these results on a conference call tomorrow, Thursday, November 2, 2023, at 8:30 a.m. Eastern Time.

Participants should register for, and access, the call using this link. While not required, it is recommended you join 10 minutes prior to the event start. Once registered, participants will be given the option to either dial into the call with the number and unique passcode provided or to use the dial-out option to connect their phone instantly.
An updated corporate presentation is available in the Investors and Media section under Presentations.
The link to access the live webcast can also be found on the Sangamo website in the Investors and Media section under Events. A replay will be available following the conference call, accessible at the same link.

On November 1, 2023 RAPT Therapeutics, Inc. (Nasdaq: RAPT), a clinical-stage, immunology-based therapeutics company focused on discovering, developing and commercializing oral small molecule therapies for patients with significant unmet needs in inflammatory diseases and oncology, reported that members of the RAPT management team will participate in the following investor conferences in November (Press release, RAPT Therapeutics, NOV 1, 2023, https://investors.rapt.com/news-releases/news-release-details/rapt-therapeutics-participate-several-upcoming-investor-3 [SID1234636653]):

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Guggenheim Healthcare Talks: 5th Annual I&I Conference – Fireside chat on Tuesday, November 7, 2023 at 3:10 p.m. ET

UBS BioPharma Conference 2023 – Fireside chat on Wednesday, November 8, 2023 at 4:00 p.m. ET

Piper Sandler 35th Annual Healthcare Conference – Fireside chat on Tuesday, November 28, 2023 at 2:30 p.m. ET

6th Annual Evercore ISI HealthCONx Conference – Fireside chat on Wednesday, November 29, 2023 at 2:35 p.m. ET

To access the available live webcasts or subsequent archived recordings of the discussions, please visit the RAPT Therapeutics website at https://investors.rapt.com/events-and-presentations.

On November 1, 2023 Prelude Therapeutics Incorporated (Prelude) (Nasdaq: PRLD), a clinical-stage precision oncology company, reported strategic pipeline updates and reports third quarter financial results (Press release, Prelude Therapeutics, NOV 1, 2023, View Source [SID1234636652]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

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Recent clinical progress and strategic prioritization of the pipeline include:

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First-in-class SMARCA2 degrader (PRT3789): Encouraging initial clinical data including selective and dose-dependent SMARCA2 degradation, safety profile and robust enrollment of biomarker-selected patients provide increased confidence in the potential of PRT3789 to address a significant clinical need.

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Potentially best-in-class CDK9 inhibitor (PRT2527): Continued demonstration of a differentiated safety profile, desired target inhibition and the opportunity in multiple hematological cancers support advancement of PRT2527 in patients with select B-cell malignancies and AML.

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MCL-1 inhibitor (PRT1419): Phase 1 dose escalation in hematological malignancies was completed. Given the overlap with the CDK9 program, Prelude does not plan to advance PRT1419 further at this time.

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CDK4/6 inhibitor (PRT3645): Phase 1 dose escalation data demonstrated plasma drug exposure and target inhibition, reaching levels needed for efficacy in preclinical models, at generally well tolerated doses. Given the focus of the Company on SMARCA2 and CDK9, Prelude will not advance the program further and is actively pursuing further clinical development with external partners.

"We made significant progress in the third quarter with our four clinical stage molecules and, as planned, conducted a rigorous assessment of each program. Based on this assessment, we are prioritizing our resources on our first-in-class SMARCA2 degrader molecules, IV and oral, and our potential best-in-class CDK9 inhibitor program," stated Kris Vaddi, Ph.D., Chief Executive Officer of Prelude. "We are confident that these two programs represent compelling opportunities for demonstrating clinical proof-of-concept in 2024, for advancing into potential Phase 2/3 registration studies, and for becoming important new medicines. This decision reflects our dual commitment to deliver differentiated treatments to patients and to build significant and sustainable value for our shareholders."

Dr. Vaddi continued, "Regarding our recently announced partnership with AbCellera, this alliance combines our strengths in small molecule drug discovery and development with AbCellera’s powerful antibody discovery engine. We plan to build a portfolio of first-in-class precision ADCs that will utilize highly selective and potent small molecules and degraders as payloads targeting critical oncogenic pathways. We have already started work on our first program with a SMARCA payload on an antibody selected from a lead panel of antibodies previously discovered by AbCellera. We believe that this program further expands the potential of our SMARCA2 selective degraders."

Jane Huang, MD, President and Chief Medical Officer, said, "Our SMARCA2 program continues to receive strong interest and support from investigators as patients with deleterious SMARCA4 mutations do not have effective treatment options. Based on our ability to select patients using a readily available biomarker, we have been able to enroll efficiently our ongoing Phase 1 clinical trial for PRT3789. We are encouraged not only by the pace of enrollment but also by early clinical data demonstrating selective degradation of SMARCA2, and by the compound’s safety profile to date. Our top priority is to generate initial clinical proof-of-concept data in 2024. Provided these results are as we expect, we anticipate advancing the compound into a registrational Phase 2/3 trial thereafter."

"For our CDK9 inhibitor PRT2527, we are also encouraged by the emerging data in both solid and hematological cancers. These data demonstrate that our highly targeted compound has been generally safe and well-tolerated with a strong inhibition of the pathway required for efficacy in preclinical models and is well-differentiated from other CDK9 inhibitors. These results strengthen our confidence in its potential best-in-class profile and position us to be the most advanced CDK9 inhibitor for patients with B-cell malignancies and AML. Our key objective is to establish clinical proof-of concept data in both the monotherapy setting and in combinations in 2024."

SMARCA Programs

PRT3789- SMARCA2 Targeted IV Protein Degrader

PRT3789 is a first-in-class highly selective degrader of SMARCA2 protein, which along with SMARCA4, controls gene regulation through chromatin remodeling. Cancer cells with SMARCA4 mutations are dependent on SMARCA2 for their growth and survival and selectively degrading SMARCA2 induces cell death in cancer cells while sparing normal cells. PRT3789 is efficacious and well-tolerated in preclinical models of SMARCA4 deleted/mutated cancers as
monotherapy and in combination with standard of care. Prelude believes a selective SMARCA2 degrader has the potential to be of benefit in up to 70,000 US/EU cancer patients with the SMARCA4 mutation.

A Phase 1 multi-dose escalation clinical trial of PRT3789 is ongoing (NCT05639751) in biomarker-selected SMARCA4 mutated cancers. Prelude intends to evaluate PRT3789 as monotherapy as well as in combination and plans to share initial Phase 1 data in mid-2024.

SMARCA2 – Oral Program

Prelude recently nominated a potent, orally bioavailable and highly selective SMARCA2 degrader candidate. This compound is >1000x selective for SMARCA2 over SMARCA4 and is currently in IND-enabling studies. Prelude expects to file an IND in the first half of 2024.

SMARCA – Precision ADC

Prelude and its partner AbCellera began work on an early-stage discovery program involving potent degraders of the SMARCA family of proteins as payloads for novel antibodies targeting tumor specific antigens. Given the potent anti-tumor activity of these molecules in pre-clinical models of cancers beyond those targeted by our SMARCA2 selective degraders, we believe that these precision ADCs have the potential to extend the therapeutic utility of this class.

CDK9 Inhibitor Program

Prelude believes its highly selective CDK9 inhibitor, PRT2527, has the potential to avoid off-target toxicities, achieve substantial clinical activity and become the best-in-class CDK9 inhibitor.

PRT2527 has completed a Phase 1 dose escalation study (NCT05159518) in patients with solid tumors. In this trial, PRT2527 was shown to achieve high levels of target inhibition and to potentially be better tolerated than existing CDK9 inhibitors, specifically manageable neutropenia and an absence of meaningful gastrointestinal events or hepatotoxicity.

The observed dose-dependent downregulation of MYC and MCL1 mRNA expression, CDK9 transcriptional targets, was consistent with the degree of target engagement required for preclinical efficacy. As predicted by the preclinical models, 12 mg/m2 QW dosing showed optimal target inhibition and has been selected as the optimal dose. The overall safety profile observed in this study supports further development of PRT2527 in hematologic malignancies (NCT05665530) and this study is currently ongoing with initial clinical data expected in mid 2024.

MCL1 Inhibitor Program

Prelude has concluded Phase 1 development of PRT1419 and established a confirmation dose in hematological cancers. Based on the potential to address the intended patient populations with the CDK9 inhibitor which potently inhibits MCL-1, Prelude has made a decision to prioritize its CDK9 inhibitor, PRT2527, over PRT1419.

Next Generation CDK4/6 Inhibitor Program

PRT3645 is a highly potent and selective next generation CDK4/6 inhibitor with the potential to provide improved safety and tolerability outcomes and to achieve higher, more effective brain and tissue penetration than current CDK4/6 inhibitors.

Prelude intends to complete the dose escalation portion of the Phase 1 clinical trial of PRT3645 this year. Prelude is actively exploring continued clinical development with external partners.

At the recent AACR (Free AACR Whitepaper)-NCI-EORTC AACR-NCI-EORTC (Free AACR-NCI-EORTC Whitepaper) International Conference on Molecular Targets and Cancer Therapeutics (EORTC-NCI-AACR) (Free ASGCT Whitepaper) (Free EORTC-NCI-AACR Whitepaper), Prelude presented data showing that treatment with PRT3645 was associated with substantial decreases in both pRb and Ki67 expression, indicating a dose-dependent target engagement at the doses evaluated. Also, PRT3645 treatment was generally well tolerated in the initial three dose cohorts of patients with no clinically meaningful gastrointestinal, hematologic or neurological events reported to date, reflecting its enhanced selectivity profile.

Third Quarter Financial Results

Cash, Cash Equivalents and Marketable Securities: Cash, cash equivalents, and marketable securities as of September 30, 2023, were $230.5 million. Prelude anticipates that its existing cash, cash equivalents and marketable securities will fund Prelude’s operations into 2026.

Research and Development (R&D) Expenses: For the third quarter of 2023, R&D expenses increased to $26.3 million from $22.9 million for the prior year period. R&D expenses increased primarily due to the timing of our clinical research programs. We expect our R&D expenses to vary from quarter to quarter, primarily due to the timing of our clinical development activities.

General and Administrative (G&A) Expenses: For the third quarter of 2023, G&A expenses decreased to $7.1 million from $7.5 million for the prior year period. G&A expenses decreased reflecting Prelude’s continued careful management of its G&A expenses.

Net Loss: For the three months ended September 30, 2023, net loss was $30.6 million, or $0.45 per share compared to $30.0 million, or $0.63 per share, for the prior year period. Included in the net loss for the quarter ended September 30, 2023, was $6.7 million of non-cash expense related to the impact of expensing share-based payments, including employee stock options, as compared to $6.4 million for the same period in 2022.