On August 5, 2021 Cardiff Oncology, Inc. (Nasdaq: CRDF), a clinical-stage oncology company, developing new precision medicine treatment options for cancer patients in indications with the greatest unmet medical need including KRAS-mutated colorectal cancer, pancreatic cancer, and castrate-resistant prostate cancer, reported recent company highlights and financial results for the second quarter ended June 30, 2021 (Press release, Cardiff Oncology, AUG 5, 2021, View Source [SID1234585854]).

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"During the past few months, we have achieved important clinical milestones that have advanced our drug development programs and further highlighted the clinical benefits of onvansertib across indications representing some of the most difficult to treat cancers" said Mark Erlander, Ph.D., chief executive officer of Cardiff Oncology. "The added expertise in drug development, financial strategy and business development brought by our CMO, CFO and new board members comes at a pivotal time for the Company, as our strong cash position and recent progress in our clinical and preclinical programs has us poised for a steady cadence of catalysts over the coming months."

Dr. Erlander continued, "Our clinical progress during the second quarter was highlighted by advancements in our two KRAS-focused programs. In metastatic pancreatic ductal adenocarcinoma (mPDAC), where approximately 95% of patients have a KRAS mutation, we began dosing patients in our Phase 2 trial evaluating onvansertib in combination with nanoliposomal irinotecan, 5-FU and leucovorin. This trial is supported by the promising data from our lead KRAS-mutated metastatic colorectal cancer program presented in April, which showed that treatment with onvansertib plus irinotecan, 5-FU and bevacizumab resulted in an overall response rate and median progression free survival that compare favorably to historical controls. Looking forward, we expect continued progress in these and our castrate-resistant prostate cancer trial as well as advancements in our efforts to expand onvansertib’s pipeline of indications."

Program highlights for the quarter ended June 30, 2021, along with recent developments, include:

Corporate Highlights:

Strengthened company leadership with the appointments of Katherine L. Ruffner, M.D., as chief medical officer (CMO) and James E. Levine as chief financial officer (CFO)

Dr. Ruffner is a US-trained hematologist/oncologist with over 25 years of clinical care, oncology biotechnology and pharmaceutical drug development experience, most recently serving as vice president, clinical development for ALX Oncology. Mr. Levine joins Cardiff Oncology with over two decades of corporate and investment banking experience in the biotechnology and pharmaceutical sectors and was most recently the chief financial officer of Cidara Therapeutics.

Added two new independent members to the Board of Directors

Mani Mohindru, Ph.D., and Renee P. Tannenbaum, Pharm.D., were appointed as independent members of Cardiff Oncology’s Board of Directors in June 2021. Dr. Mohindru is an experienced biotech industry executive and is currently the chief executive officer of Novasenta, an early-stage biotechnology company, and a director on the Board of CytomX, Inc., a clinical-stage biopharmaceutical company. Dr. Tannenbaum currently serves as vice president of global partnering at Halozyme, Inc. and has in-depth expertise in business development and in establishing successful strategic partnerships.

Added as a member of FTSE Russell Indexes

As of the market open on June 28, 2021, Cardiff Oncology was included as a member of the small-cap Russell 2000 Index, the all-cap Russell 3000 Index, and the Russell Microcap Index.

KRAS-mutated Metastatic Colorectal Cancer (mCRC) Program:

Announced the upcoming presentation of new data from lead clinical program in KRAS-mutated mCRC on Wednesday, September 8, 2021

Updated data from the Phase 1b/2 trial evaluating onvansertib in combination with standard-of-care FOLFIRI/bevacizumab for the second-line treatment of patients with KRAS-mutated mCRC will be announced at a webinar on September 8, 2021 at 4:00 p.m. ET featuring the clinical trial principal investigator, Heinz-Josef Lenz, M.D., FACP (USC Norris Comprehensive Cancer Center), and key clinical advisor Afsaneh Barzi, M.D., Ph.D., (City of Hope Comprehensive Cancer Center). To register for the webinar, click here.

Announced updated data from the Phase 1b/2 trial evaluating onvansertib plus FOLFIRI/bevacizumab that continues to demonstrate robust response to treatment and progression-free survival in KRAS-mutated mCRC

The data were presented as part of a Key Opinion Leader webinar in April featuring Daniel H. Ahn, D.O., M.S. (Mayo Clinic Arizona), and Manish R. Sharma, M.D. (START Midwest), and showed robust patient response and progression-free survival when onvansertib is combined with standard-of-care therapy in second line KRAS-mutated mCRC. Data highlights from the Phase 1b trial, as of April 4, 2021, include:

7 of 18 (39%) evaluable patients achieved a partial response (PR)
Evaluable patients have a median progression free survival (mPFS) of 9.4 months (95% confidence interval: 7.85 months – not reached), more than double the historical 4.5-month mPFS from analysis of 23 randomized trials in second-line metastatic colorectal cancer (data from ~10,800 patients)¹
7 patients remain on treatment
Clinical responses were observed across different KRAS mutations, including the 3 most common in colorectal cancer (G12D, G12V, G13D)
The greatest decreases in plasma KRAS mutant allelic frequency (MAF) after 1 cycle of treatment were observed in patients achieving a PR
Onvansertib in combination with FOLFIRI/bevacizumab has been well tolerated with no major or unexpected toxicities attributed to onvansertib
Presented findings from the Expanded Access Program (EAP) for onvansertib in KRAS-mutated mCRC highlighting the clinical benefit of onvansertib in heavily pretreated patients

Findings from 20 evaluable EAP participants who were heavily pre-treated (median of 3 prior lines of treatment) were presented at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2021 in April. Participants enrolled in the EAP had failed or progressed on multiple lines of standard-of-care treatment and were treated with the same combination regimen (onvansertib 15 mg/m2 + FOLFIRI/bevacizumab) and dosing schedule used in the ongoing Phase 1b/2 mCRC clinical trial. Highlights from the AACR (Free AACR Whitepaper) presentation included:

15 of 20 (75%) evaluable participants received an irinotecan-based regimen as their last therapy prior to enrolling in the EAP.
13 of 20 (65%) evaluable participants were progressing prior to enrolling in the EAP
Median progression free survival (mPFS) was 5.6 months (95% confidence interval: 2.7 months – not reached), which is significantly greater than historical controls (2-3 months)2
62.5% of participants had a greater than 50% decrease in KRAS MAF after one cycle of treatment and continue to show a durable response and have not reached mPFS
11 of 20 of evaluable participants remain on treatment
Onvansertib in combination with FOLFIRI/bevacizumab has been well tolerated with no serious adverse events (SAEs) reported
Metastatic Pancreatic Ductal Adenocarcinoma (mPDAC) Program:

Began dosing patients in the Phase 2 trial of onvansertib in metastatic PDAC

The trial is a key component of onvansertib’s KRAS-targeted clinical programs and is designed to assess the safety and preliminary efficacy of onvansertib in combination with nanoliposomal irinotecan (Onivyde), leucovorin and fluorouracil (5-FU) as a second-line treatment in patients with metastatic PDAC who have failed first-line gemcitabine-based therapy. The trial expects to enroll 40 patients at 6 U.S. sites. Onvansertib’s potential in mPDAC, where ~95% of patients have a KRAS mutation, is supported by the promising clinical data seen in KRAS-mutated mCRC patients treated with the combination of onvansertib, irinotecan and 5-FU (FOLFIRI).

Metastatic Castrate-Resistant Prostate Cancer (mCRPC) Program:

Identified an androgen-independent mechanism of synergy between onvansertib and abiraterone in mCRPC

Collaborative studies with the Massachusetts Institute of Technology featured in a virtual oral poster presentation at the AACR (Free AACR Whitepaper) Annual Meeting 2021 suggest that the androgen receptor signaling inhibitor abiraterone sensitizes certain prostate cancer cells to onvansertib via the induction of a mitosis related gene signature and disruption of mitotic spindle orientation. These results are consistent with previous findings showing that onvansertib and abiraterone synergize in an androgen receptor-independent manner in vitro and in vivo. Data from the studies also suggest that the identified mitosis related gene signature may be predictive of patient response to onvansertib-abiraterone combination therapy, a hypothesis that is being further assessed in the ongoing Phase 2 mCRPC trial.

Second Quarter 2021 Financial Results:

As of June 30, 2021, Cardiff Oncology had approximately $140 million in cash, cash equivalents and short-term investments.

Total operating expenses were approximately $7.0 million for the three months ended June 30, 2021, an increase of $2.9 million from $4.1 million for the same period in 2020. The increase in operating expenses is attributed to ongoing and new onvansertib clinical development programs and preclinical activities, additional outside services for legal fees mainly related to the expansion of our patent portfolio, recruiting fees and stock compensation expense.

Research and development expenses increased by approximately $1.6 million to $4.1 million for the three months ended June 30, 2021, from $2.5 million for the same period in 2020. The increase in research and development expenses was primarily due to advancing the onvansertib clinical and preclinical programs and recruitment fees to fill the critical position of chief medical officer.

Selling, general and administrative expenses increased by approximately $1.1 million to $2.8 million for the three months ended June 30, 2021, from $1.7 million for the same period in 2020. The increase is attributed to increased outside services for legal fees related to the expansion of our patent portfolio, recruitment fees, and stock compensation expense.

Net cash used in operating activities in the second quarter of 2021 was approximately $4.3 million, which is comparable to the $4.3 million for the same period in 2020.

On August 5, 2021 Sangamo Therapeutics, Inc. (Nasdaq: SGMO), a genomic medicine company, today reported recent business highlights and second quarter 2021 financial results.

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"This is an exciting time at Sangamo, as we look forward to multiple clinical catalysts over the next several quarters representing potential near-term value drivers, while we continue to advance our promising preclinical pipeline focused on the emerging areas of CAR-Tregs and transcriptional regulation, representing potential mid-term value drivers"

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"This is an exciting time at Sangamo, as we look forward to multiple clinical catalysts over the next several quarters representing potential near-term value drivers, while we continue to advance our promising preclinical pipeline focused on the emerging areas of CAR-Tregs and transcriptional regulation, representing potential mid-term value drivers," said Sandy Macrae, Chief Executive Officer of Sangamo.

Recent Business Highlights

We dosed a fourth patient in our wholly-owned Phase 1/2 STAAR study evaluating ST-920 gene therapy for Fabry disease, completing dosing of the second cohort. Based on initial safety data from patients dosed to date, the Safety Monitoring Committee recommended dose escalating to the third dose as planned under the study protocol. We are currently screening patients for the third dose cohort.
Biogen selected a fourth neurological disease gene target under our collaboration agreement, and we have begun early research activities on therapies addressing this target.
We appointed Prathyusha Duraibabu as Chief Financial Officer and Scott Willoughby as General Counsel and Corporate Secretary.
Second Quarter 2021 Financial Results

Consolidated net loss attributable to Sangamo for the second quarter ended June 30, 2021 was $47.2 million or $0.33 per share, compared to a net loss attributable to Sangamo of $35.9 million or $0.26 per share for the same period in 2020.

Revenues

Revenues for the second quarter ended June 30, 2021 were $27.9 million, compared to $21.6 million for the same period in 2020.

The increase of $6.3 million in revenues was primarily due to the recognition of upfront license fees and research revenue of $9.6 million under our collaboration agreement with Novartis and $2.6 million higher revenue related to our collaboration agreement with Biogen. These increases were partially offset by a decrease of $3.8 million in research revenue related to our giroctocogene fitelparvovec and C9ORF72 collaboration agreements with Pfizer, due to completion of our activities under these collaborations, a decrease of $1.1 million in research revenue related to our collaboration agreement with Kite, and a decrease of $0.9 million in research revenue related to our collaboration agreement with Sanofi.

GAAP and Non-GAAP operating expenses

Total operating expenses on a GAAP basis for the second quarter ended June 30, 2021 were $76.6 million compared to $59.4 million for the same period in 2020. Non-GAAP operating expenses, which exclude stock-based compensation expense, for the second quarter ended June 30, 2021 were $67.1 million compared to $52.7 million for the same period in 2020.

The increase in total operating expenses on a GAAP basis was primarily driven by our higher clinical and manufacturing supply expenses along with our increased headcount to support the advancement of our clinical trials and our new collaborations.

Cash, cash equivalents and marketable securities

Cash, cash equivalents and marketable securities as of June 30, 2021 were $578.9 million compared to $692.0 million as of December 31, 2020.

Guidance for 2021 Reiterated (initial guidance provided on February 24, 2021)

On a GAAP basis, we expect total operating expenses, including non-cash stock-based compensation expenses, to be in the range of approximately $285 million to $305 million for the year ended December 31, 2021.

On a non-GAAP basis, we expect total operating expenses, excluding estimated non-cash stock-based compensation expense of approximately $30 million, to be in the range of approximately $255 million to $275 million for the year ended December 31, 2021.

Conference Call

Sangamo will host a conference call today, August 5, 2021, at 4:30 p.m. Eastern Time, which will be open to the public. The call will also be webcast with live Q&A and can be accessed via a link on the Sangamo Therapeutics website in the Investors and Media section under Events and Presentations.

The conference call dial-in numbers are (877) 377-7553 for domestic callers and (678) 894-3968 for international callers. The conference ID number for the call is 1971045. Participants may access the live webcast via a link on the Sangamo Therapeutics website in the Investors and Media section under Events and Presentations. A conference call replay will be available for one week following the conference call. The conference call replay numbers for domestic and international callers are (855) 859-2056 and (404) 537-3406, respectively. The conference ID number for the replay is 1971045.

On August 5, 2021 Quanterix Corporation (NASDAQ:QTRX), a company digitizing biomarker analysis to advance the science of precision health, reported financial results for the three months ending June 30, 2021 (Press release, Quanterix, AUG 5, 2021, View Source [SID1234585886]).

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"The past quarter has proven to be a pivotal time for our company as we continue to make immense strides with our strategic expansion in the diagnostics space," said Kevin Hrusovsky, Chairman and Chief Executive Officer, Quanterix. "With drug advances taking place for neurodegenerative diseases, there is a heightened focus to diagnose and detect cognitive conditions like Alzheimer’s Disease as early as possible and then to monitor disease progression in the patient once a drug agent is deployed. We are a leader in this area and improving outcomes and helping advance methodologies to enhance coverage with evidence for payers will change the way disease is studied, drugs are approved and ultimately how care is delivered economically and effectively."

Second Quarter 2021 Financial Highlights

Key financial results for the second quarter of 2021 are shown below:

Q2 GAAP total revenue, which includes grant revenue of $0.9M, was $25.4M versus prior year Q2 of $13.1M, an increase of 93%;
Q2 non-GAAP total revenue was $24.4M versus prior year Q2 of $13.1M, an increase of 86%;
Q2 GAAP product revenue was $18.7M versus prior year Q2 of $6.8M, an increase of 175%;
Q2 GAAP service and other revenue was $5.6M versus prior year Q2 of $6.3M, a decrease of 11%;
Q2 GAAP gross margin was 54.7% versus prior year Q2 of 39.7%, an increase of 1,500 bps; Q2 non-GAAP gross margin was 55.1% versus prior year Q2 of 44.1%, an increase of 1,100 bps
1H 2021 Financial Highlights

Key financial results for the first half of 2021 are shown below:

1H GAAP total revenue, which includes grant revenue of $3.2M, was $52.6M versus prior year 1H of $28.9M, an increase of 82%;
1H non-GAAP total revenue was $49.3M versus prior year 1H of $28.9M, an increase of 71%;
1H GAAP product revenue was $36.9M versus prior year 1H of $16.6M, an increase of 122%;
1H GAAP service and other revenue was $12.1M, consistent with prior year 1H of $12.1M;
1H GAAP gross margin was 57.5% versus prior year 1H of 41.7%; 1H non-GAAP gross margin was 56.8% versus prior year 1H of 46.5%, an increase of 1,030 bps
For additional information on the non-GAAP financial measures included in this press release, please see "Use of Non-GAAP Financial Measures" and "Reconciliation of Non-GAAP Financials" below.

Second Quarter 2021 Business Highlights

Record Product Revenue of $18.7M for Q2 2021, an increase of 175% versus prior year Q2.
FDA approval of Biogen’s Aducanamab underscores potential of plasma-based neuro biomarkers in drug development and diagnostics.
Quanterix’ Simoa technology powered the largest and most diverse global investigation of the role of plasma neurofilament light (NfL) in dementia diagnosis, published in Nature Communications. The research marks the most robust effort to date to assess the use of NfL in blood to screen for neurodegeneration as a cause of cognitive symptoms; differentiate among neurodegenerative disorders and distinguish psychiatric disorders; and derive age-related concentration cutoffs that may help to maximize plasma NfL’s usefulness in a clinical setting.
Delivered a virtual presentation at the Goldman Sachs 42nd Annual Global Healthcare Conference on June 10 and appeared on the June 3 episode of The Bio Report, a leading podcast that focuses on the intersection of biotechnology and business, science, and policy to discuss the implications of biomarkers on the future of drug development and diagnostics.
Hosted the webinar: Recent Advancements in Neurodegenerative Biomarkers: Progress Towards a Diagnostic Blood Test for Alzheimer’s Disease that featured leading industry experts to discuss neurological advancements related to the ultra-sensitive quantification of pTau181, pTau217, pTau231, and other neurological biomarkers.
Welcomed Masoud Toloue, an industry expert from PerkinElmer, to the position of President of Quanterix and Diagnostics to lead Quantertix’ growing diagnostics business and assume responsibility for the Company’s Accelerator Lab Services, strategic partnerships and corporate development.
Appointed Michael Doyle, a strong financial executive with deep public company experience to the position of Chief Financial Officer (CFO) and Treasurer.
Quanterix Simoa technology was highlighted in 130 new publications, bringing total Simoa-specific inclusions to more than 1,300 publications.
Conference Call
In conjunction with this announcement, Quanterix Corporation will host a conference call on August 5 at 4:30pm EDT. Individuals interested in listening to the conference call may do so by dialing 833-686-9351 for domestic callers, or 612-979-9890 for international callers. Please reference the following conference ID: 2299526.

A live webcast will also be available at: View Source The webcast will be available on the Company’s website, View Source, for one year following completion of the call.

Financial Highlights (in thousands)

Use of Non-GAAP Financial Measures
To supplement the Company’s financial statements presented on a GAAP basis, the Company has provided certain non-GAAP financial measures, including non-GAAP revenue and non-GAAP gross margin. Management uses these non-GAAP measures to evaluate the Company’s operating performance in a manner that allows for meaningful period-to-period comparison and analysis of trends in its business. Management believes that such measures are important in comparing current results with prior period results and are useful to investors and financial analysts in assessing the Company’s operating performance. The non-GAAP financial information presented here should be considered in conjunction with, and not as a substitute for, the financial information presented in accordance with GAAP. Investors are encouraged to review the reconciliation of these non-GAAP measures to their most directly comparable GAAP financial measures set forth below.

On August 5, 2021 Karyopharm Therapeutics Inc. (Nasdaq:KPTI), a commercial-stage pharmaceutical company pioneering novel cancer therapies, reported business highlights and financial results for the quarter ended June 30, 2021 (Press release, Karyopharm, AUG 5, 2021, View Source [SID1234585902]).

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Richard Paulson, President and Chief Executive Officer of Karyopharm, commented, "We are encouraged by the commercial performance of XPOVIO during the first half of 2021, which reflected meaningful year-over-year growth, up 21% compared to the first half of 2020, driven by rising confidence and demand from both academic and community-based oncologists. XPOVIO continues to move earlier in the treatment paradigm following U.S. Food and Drug Administration (FDA) approval in the second-line plus treatment setting for multiple myeloma in December 2020. In my first 100 days as CEO, my top priorities have been executional excellence in our multiple myeloma launch and prioritizing and advancing our pipeline. With respect to the launch, we’ve strengthened our organization and execution while solidifying our positioning in the multiple myeloma treatment landscape. XPOVIO is a new and effective modality that can become a standard of care in second-line plus, where utilizing new mechanisms is critical to continue improving patient outcomes. With respect to the pipeline, we have initiated a comprehensive portfolio review and continue to move forward with key new trials."

"Looking ahead to the remainder of 2021, there are several important events and milestones on the horizon. First, we plan to host an investor day in the fourth quarter to outline Karyopharm’s commercial and pipeline priorities and objectives for the upcoming quarters and years. Next, along with continued commercial growth in hematologic cancers, we are expecting top-line data from the Phase 3 SIENDO study in endometrial cancer, also around the end of this year. Endometrial cancer is the most common gynecologic cancer and has the potential to be our first XPOVIO approval in solid tumors. And finally, we expect to initiate or expand several key clinical studies across our pipeline, including in myelodysplastic syndrome, myelofibrosis, multiple myeloma and colorectal cancer," concluded Mr. Paulson.

Second Quarter 2021 & Recent Highlights

XPOVIO Commercial Performance

Achieved U.S. net product revenue for the second quarter of 2021 of $20.2 million and $41.9 million year to date, representing 8% growth compared to the second quarter of 2020 and 21% growth compared to the first half of 2020.
Achieved the following across both multiple myeloma and diffuse large B-cell lymphoma (DLBCL):
Over 7,600 prescriptions filled as of June 30, 2021; and
Added 142 new unique accounts during the second quarter of 2021, an increase of 11% compared to the first quarter of 2021.
Payer coverage remains strong at 97%.
Launched three new strength oral XPOVIO tablets (40mg, 50mg and 60mg), versus only 20mg available previously, to simplify regimens and reduce pill burden for patients.
Intent to prescribe metrics show a rising confidence in physicians’ overall perception of XPOVIO and that physicians are choosing it for earlier lines of treatment; discontinuation rates remain low (approximately 13%).
Strengthened the commercial team with the appointment of Sohanya Cheng, former sales and marketing lead for Kyprolis (carfilzomib) at Amgen, as Head of Sales and Commercial Operations.
Expanded global access to XPOVIO through the conditional approval for XPOVIO plus dexamethasone in the United Kingdom for the treatment of penta-refractory multiple myeloma, and Karyopharm’s partner Antengene securing marketing approval for XPOVIO for the treatment of penta-refractory multiple myeloma and DLBCL in South Korea.
R&D Highlights

Hematologic Malignancies: Karyopharm is actively building its hematologic oncology franchise through several key initiatives, including pursuing NEXPOVIO marketing approval in Europe in the second-line plus treatment setting for multiple myeloma, expanding approved multiple myeloma indications in the U.S. to include combinations with certain approved therapies, and pursuing additional high unmet need indications beyond multiple myeloma, such as myelofibrosis and myelodysplastic syndrome.

European Medicines Agency (EMA) validated the Marketing Authorization Application (MAA) for NEXPOVIO in combination with Velcade (bortezomib) and low-dose dexamethasone for the treatment of multiple myeloma following at least one prior therapy. The MAA will be reviewed by the Committee for Medicinal Products for Human Use (CHMP), which will issue an opinion to the European Commission regarding the potential approval for the expanded indication. Karyopharm expects this review to be completed in the first half of 2022.
Presented positive results for near-term and longer-term multiple myeloma expansion programs at the European Hematology Association (EHA) (Free EHA Whitepaper) 2021 Congress, including:
The arm of the Phase 1b/2 STOMP study evaluating the all oral combination of XPOVIO, Pomalyst (pomalidomide) and dexamethasone (XPd) in previously treated multiple myeloma. Karyopharm remains on track to initiate a randomized Phase 3 study with this combination by the end of 2021.
A subset analysis demonstrating that two STOMP triplet regimens XPOVIO, Kyprolis and dexamethasone (XKd) and XPd achieved high response rates of 67% and 58%, respectively, in multiple myeloma patients with disease refractory to an anti-CD38 monoclonal antibody. These response rates compare favorably to the ~45% response rates seen with other combo regimens.
Commenced dosing in a new Phase 1/2 study evaluating XPOVIO in combination with Jakafi (ruxolitinib) in patients with treatment-naïve myelofibrosis (XPORT-MF-034; NCT04562389).
XPOVIO in Solid Tumors: In 2020, Karyopharm established proof-of-concept for XPOVIO in solid tumors in advanced liposarcoma. The Company is actively pursuing additional solid tumor indications for XPOVIO, either alone or in combination with other agents, including in endometrial cancer, glioblastoma, melanoma, colorectal cancer and non-small cell lung cancer.

Continued enrollment and dosing in the Phase 3 SIENDO study. Remain on track to report top-line results during the fourth quarter of 2021.
Commenced dosing in a new Phase 2 study evaluating XPOVIO in combination with Keytruda (pembrolizumab) in patients with locally advanced or metastatic melanoma (XPORT-MEL-033; NCT04768881).
Corporate & Business Highlights

Richard Paulson, formerly of Ipsen North American and Amgen, named President and Chief Executive Officer.
Received $60 million in expanded royalty agreement with entities managed by HealthCare Royalty Management, LLC (HCR), with up to another $40 million in potential financing available.
Acquired investigational Interleukin-12 (IL-12) program from Neumedicines Inc. for $7.4 million in cash and equity and certain other contingent consideration upon the satisfaction of certain development milestones. Karyopharm is evaluating potential opportunities to combine IL-12 asset with XPOVIO and/or other therapies for cancer and other diseases.
Karyopharm to host an investor day during the fourth quarter of 2021 to outline commercial and pipeline priorities and objectives.
Second Quarter 2021 Financial Results

"Our balance sheet remains strong, and based on our current operating plans, we believe our cash, cash equivalents and investments, together with growing XPOVIO revenues, license revenues and the recent capital secured through our amended agreement with HCR, provide us with a cash runway into mid-2023," said Michael P. Mason, Chief Financial Officer of Karyopharm. "Through steady topline growth, driven by both increased physician adoption as well as adding new patient groups and indications over time, our goal is to become a self-sustaining organization for our stakeholders."

Net product revenue: Net product revenue for the second quarter of 2021 was $20.2 million, compared to $18.6 million for the second quarter of 2020.

License and other revenue: License and other revenue for the second quarter of 2021 was $2.4 million, compared to $14.9 million for the second quarter of 2020. During the three months ended June 30, 2021, Karyopharm recognized $1.0 million pursuant to its license agreement with Anivive Lifesciences, Inc. and $1.4 million of revenue associated with named patient programs. During the three months ended June 30, 2020, Karyopharm recognized $12.7 million pursuant to its license agreement with Antengene Therapeutics Limited and $2.2 million upon reacquisition of the exclusive development and commercial rights from Ono Pharmaceutical Co., Ltd.

Cost of sales: Cost of sales for the second quarter of 2021 were $1.1 million, compared to $0.4 million for the second quarter of 2020. Cost of sales reflects the costs of XPOVIO units sold and third-party royalties on net product revenue.

Research and development (R&D) expenses: R&D expenses for the second quarter of 2021 were $34.0 million, compared to $42.6 million for the second quarter of 2020. The decrease in R&D expenses in the second quarter of 2021 compared to the second quarter of 2020 was primarily attributable to the COVID-19 trial activity in the second quarter of 2020 that did not occur in 2021.

Selling, general and administrative (SG&A) expenses: SG&A expenses for the second quarter of 2021 were $36.5 million, compared to $30.8 million for the second quarter of 2020. The increase in SG&A expenses in the second quarter of 2021 compared to the second quarter of 2020 was due primarily to activities to support the U.S. commercialization of XPOVIO, including the launch of XPOVIO in combination with once-weekly Velcade and dexamethasone for the treatment of adult patients with multiple myeloma who have received at least one prior therapy.

Interest expense: Interest expense for the second quarter of 2021 was $5.0 million, compared to $6.8 million for the second quarter of 2020. The decrease in interest expense was primarily attributable to the decrease in non-cash interest expense related to Karyopharm’s 3.00% senior convertible notes due 2025, as a result of the January 1, 2021 adoption of ASU No. 2020-06, Debt—Debt with Conversion and Other Options and Derivatives and Hedging—Contracts in Entity’s Own Equity. Post adoption, Karyopharm is no longer required to amortize the debt discount to non-cash interest expense, as the debt discount component of $50.6 million has now been reclassified out of equity into the convertible senior notes line on its balance sheet.

Net loss: Karyopharm reported a net loss of $53.6 million, or $0.71 per share, for the second quarter of 2021, compared to a net loss of $46.4 million, or $0.63 per share, for the second quarter of 2020. Net loss included non-cash stock-based compensation expense of $8.1 million and $6.4 million for the second quarters of 2021 and 2020, respectively.

Cash position: Cash, cash equivalents, restricted cash and investments as of June 30, 2021 totaled $239.3 million, compared to $276.7 million as of December 31, 2020.

2021 Financial Outlook

Based on its current operating plans, Karyopharm expects the following for full year 2021:

Non-GAAP R&D and SG&A expenses, excluding stock-based compensation expense, are expected to be in the range of $270 million to $290 million. Karyopharm has not reconciled the full year 2021 outlook for non-GAAP R&D and SG&A expenses to full year 2021 outlook for GAAP R&D and SG&A expenses because Karyopharm cannot reliably predict without unreasonable efforts the timing or amount of the factors that substantially contribute to the projection of stock compensation expense, which is excluded from the full year 2021 outlook for non-GAAP R&D and SG&A expenses.
The Company expects that its existing cash, cash equivalents and investments, together with the revenue it expects to generate from XPOVIO product sales, as well as revenue generated from its license agreements, will be sufficient to fund its planned operations into the middle of 2023.
Non-GAAP Financial Information

Karyopharm uses a non-GAAP financial measure, including R&D and SG&A expenses, to provide operating expense guidance. Non-GAAP R&D and SG&A expenses exclude stock-based compensation expense. Karyopharm believes this non-GAAP financial measure is useful to investors because it provides greater transparency regarding Karyopharm’s operating performance as it excludes non-cash stock compensation expense. This non-GAAP financial measure should not be considered a substitute or an alternative to GAAP R&D and SG&A expenses and should not be considered a measure of Karyopharm’s liquidity. Instead, non-GAAP R&D and SG&A expenses should only be used to supplement an understanding of Karyopharm’s operating results as reported under GAAP.

Conference Call Information

Karyopharm will host a conference call today, Thursday, August 5, 2021, at 8:30 a.m. Eastern Time, to discuss the second quarter 2021 financial results and other company updates. To access the conference call, please dial (888) 437-3179 (local) or (862) 298-0702 (international) at least 10 minutes prior to the start time and ask to be joined into the Karyopharm Therapeutics call. A live audio webcast of the call will be available under "Events & Presentations" in the Investor section of the Company’s website, View Source An archived webcast will be available on the Company’s website approximately two hours after the event.

About XPOVIO (selinexor)

XPOVIO is a first-in-class, oral Selective Inhibitor of Nuclear Export (SINE) compound. XPOVIO functions by selectively binding to and inhibiting the nuclear export protein exportin 1 (XPO1, also called CRM1). XPOVIO blocks the nuclear export of tumor suppressor, growth regulatory and anti-inflammatory proteins, leading to accumulation of these proteins in the nucleus and enhancing their anti-cancer activity in the cell. The forced nuclear retention of these proteins can counteract a multitude of the oncogenic pathways that, unchecked, allow cancer cells with severe DNA damage to continue to grow and divide in an unrestrained fashion. Karyopharm received accelerated U.S. Food and Drug Administration (FDA) approval of XPOVIO in July 2019 in combination with dexamethasone for the treatment of adult patients with relapsed refractory multiple myeloma (RRMM) who have received at least four prior therapies and whose disease is refractory to at least two proteasome inhibitors, at least two immunomodulatory agents, and an anti-CD38 monoclonal antibody. NEXPOVIO (selinexor) has also been granted conditional marketing authorization for adult patients with heavily pretreated multiple myeloma by the European Commission. Karyopharm’s supplemental New Drug Application (sNDA) requesting an expansion of its indication to include the treatment for patients with multiple myeloma after at least one prior therapy was approved by the FDA on December 18, 2020. In June 2020, Karyopharm received accelerated FDA approval of XPOVIO for its second indication in adult patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL), not otherwise specified, including DLBCL arising from follicular lymphoma, after at least 2 lines of systemic therapy. Selinexor is also being evaluated in several other mid-and later-phase clinical trials across multiple cancer indications, including as a potential backbone therapy in combination with approved myeloma therapies (STOMP) and in endometrial cancer (SIENDO), among others. Additional Phase 1, Phase 2 and Phase 3 studies are ongoing or currently planned, including multiple studies in combination with approved therapies in a variety of tumor types to further inform Karyopharm’s clinical development priorities for selinexor. Additional clinical trial information for selinexor is available at www.clinicaltrials.gov.

For more information about Karyopharm’s products or clinical trials, please contact the Medical Information department at:

Tel: +1 (888) 209-9326
Email: [email protected]

XPOVIO (selinexor) is a prescription medicine approved:

In combination with bortezomib and dexamethasone for the treatment of adult patients with multiple myeloma who have received at least one prior therapy (XVd).
In combination with dexamethasone for the treatment of adult patients with relapsed or refractory multiple myeloma who have received at least four prior therapies and whose disease is refractory to at least two proteasome inhibitors, at least two immunomodulatory agents, and an anti–CD38 monoclonal antibody (Xd).
For the treatment of adult patients with relapsed or refractory diffuse large B–cell lymphoma (DLBCL), not otherwise specified, including DLBCL arising from follicular lymphoma, after at least 2 lines of systemic therapy. This indication is approved under accelerated approval based on response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trial(s).
SELECT IMPORTANT SAFETY INFORMATION

Warnings and Precautions

Thrombocytopenia: Monitor platelet counts throughout treatment. Manage with dose interruption and/or reduction and supportive care.
Neutropenia: Monitor neutrophil counts throughout treatment. Manage with dose interruption and/or reduction and granulocyte colony–stimulating factors.
Gastrointestinal Toxicity: Nausea, vomiting, diarrhea, anorexia, and weight loss may occur. Provide antiemetic prophylaxis. Manage with dose interruption and/or reduction, antiemetics, and supportive care.
Hyponatremia: Monitor serum sodium levels throughout treatment. Correct for concurrent hyperglycemia and high serum paraprotein levels. Manage with dose interruption, reduction, or discontinuation, and supportive care.
Serious Infection: Monitor for infection and treat promptly.
Neurological Toxicity: Advise patients to refrain from driving and engaging in hazardous occupations or activities until neurological toxicity resolves. Optimize hydration status and concomitant medications to avoid dizziness or mental status changes.
Embryo–Fetal Toxicity: Can cause fetal harm. Advise females of reproductive potential and males with a female partner of reproductive potential, of the potential risk to a fetus and use of effective contraception.
Cataract: Cataracts may develop or progress. Treatment of cataracts usually requires surgical removal of the cataract.
Adverse Reactions

The most common adverse reactions (≥20%) in patients with multiple myeloma who receive XVd are fatigue, nausea, decreased appetite, diarrhea, peripheral neuropathy, upper respiratory tract infection, decreased weight, cataract and vomiting. Grade 3–4 laboratory abnormalities (≥10%) are thrombocytopenia, lymphopenia, hypophosphatemia, anemia, hyponatremia and neutropenia. In the BOSTON trial, fatal adverse reactions occurred in 6% of patients within 30 days of last treatment. Serious adverse reactions occurred in 52% of patients. Treatment discontinuation rate due to adverse reactions was 19%.
The most common adverse reactions (≥20%) in patients with multiple myeloma who receive Xd are thrombocytopenia, fatigue, nausea, anemia, decreased appetite, decreased weight, diarrhea, vomiting, hyponatremia, neutropenia, leukopenia, constipation, dyspnea and upper respiratory tract infection. In the STORM trial, fatal adverse reactions occurred in 9% of patients. Serious adverse reactions occurred in 58% of patients. Treatment discontinuation rate due to adverse reactions was 27%.
The most common adverse reactions (incidence ≥20%) in patients with DLBCL, excluding laboratory abnormalities, are fatigue, nausea, diarrhea, appetite decrease, weight decrease, constipation, vomiting, and pyrexia. Grade 3–4 laboratory abnormalities (≥15%) are thrombocytopenia, lymphopenia, neutropenia, anemia, and hyponatremia. In the SADAL trial, fatal adverse reactions occurred in 3.7% of patients within 30 days, and 5% of patients within 60 days of last treatment; the most frequent fatal adverse reactions was infection (4.5% of patients). Serious adverse reactions occurred in 46% of patients; the most frequent serious adverse reaction was infection (21% of patients). Discontinuation due to adverse reactions occurred in 17% of patients.
Use In Specific Populations

Lactation: Advise not to breastfeed.

On August 5, 2021 Portage Biotech Inc., (NASDAQ: PRTG) ("Portage" or the "Company") a clinical-stage immuno-oncology company focused on the development of therapies targeting cancer treatment resistance, reported that the first patient has been dosed in the Oxford-led IMP-MEL study, a Phase 1/2, open-label, dose-escalation and randomized expansion clinical trial assessing the safety, tolerability and efficacy of PORT-2, a liposome formulation of the invariant natural killer T-cell (iNKT) agonist IMM60 developed for the treatment of solid tumors (Press release, Portage Biotech, AUG 5, 2021, View Source [SID1234585917]).

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Preclinical data for PORT-2 demonstrated good tolerability and a strong cancer-specific B- and T-cell response. It also showed a robust innate and adaptive immune response and an increase in expression of PD-L1 on cancer cells. Combining PORT-2 with checkpoint inhibitors led to increased immune activation and PD-L1 expression, suggesting rationale for enhanced activity of the combination treatment.

"PORT-2 offers a novel, targeted approach to address a variety of today’s most common cancers, many of which are often elusive or resistant to treatment. Preclinical data show that our iNKT agonist can stimulate a broad response from both the innate and adaptive immune systems, helping the body recognize and attack these cancers," said Dr. Ian Walters, chief executive officer of Portage Biotech. "This first-in-human trial features a robust design with a multi-arm comparison against standard of care therapies currently used in the clinic, which we believe has the potential to accelerate our research as we evaluate the effectiveness of PORT-2 both as a monotherapy and in combination with PD-1 checkpoint inhibitors."

The IMP-MEL study is expected to enroll 100 patients at Oxford and other centers and will evaluate PORT-2 both as a monotherapy and in combination with approved PD-1 inhibitor Keytruda in the treatment of Melanoma and Non-Small Cell Lung Cancer (NSCLC).

"Checkpoint inhibitor therapies have enormous opportunity in the treatment of solid tumors, but unfortunately, many cancers develop a resistance to these therapies leaving many patients without adequate treatment options," said Mark Middleton, Departmental Head of Oncology and Professor of Experimental Medicine at the University of Oxford. "We’re constantly seeking new therapies that are capable of addressing resistance and enabling a durable response in patients with cancer. Should PORT-2 prove successful, this novel iNKT agonist therapy could potentially re-sensitize patients to checkpoint inhibitor treatment and could activate that durable immune response. It’s a very exciting new avenue for oncology research."

The IMP-MEL study is part of a comprehensive clinical development plan to evaluate Portage’s iNKT agonist therapies, PORT-2 and PORT-3. PORT-3, which is a nanoparticle co-formulation of IMM60 and a NY-ESO-1 peptide antigen, is also currently being evaluated in a Phase 1 clinical trial initiated in April 2021 at Radboud University, Netherlands.

The IMP-MEL study is supported by the NIHR Biomedical Research Centre. The trial is actively recruiting at the University of Oxford, United Kingdom. For more information, please visit View Source #ISRCTN80472712

About iNKT agonists PORT-2 and PORT-3

PORT-2 and PORT-3 contain small molecule agonists (IMM60) of invariant natural killer T-cells (iNKT cells) developed by the University of Oxford, which play an important role in anti-tumor immune responses. iNKT cells are a distinct class of T lymphocytes and recognize lipid antigens on the surface of the tumor. Our synthetic iNKT agonists are designed to optimally engage the T-cell receptor on the iNKT and facilitate its binding to dendritic cells, resulting in the secretion of a large amount of pro-inflammatory cytokines. This leads to the activation and expansion of important immune system components and primes and boosts an adaptive immune attack against cancer. We see that monotherapy treatment with iNKT agonists shows a heightened immune response and better cancer control in animal models that are resistant to PD-1 antibody treatment. Combination therapy with PD-1 antibodies is synergistic with iNKT agonists and restores sensitivity to PD-1 blockade. While treatment with iNKT agonists alone shows promising preclinical activity against cancer, data suggests that when an iNKT agonist is co-packaged with tumor-specific antigens, potency is increased by up to 5x. PORT-2 is a liposomal formulation of our IMM60 iNKT agonist while PORT-3 is a co-formulation of our IMM60 iNKT agonist with an NY-ESO-1 peptide vaccine, co-packaged into a nanoparticle.