On August 4, 2022 Bicycle Therapeutics plc (NASDAQ: BCYC), a biotechnology company pioneering a new and differentiated class of therapeutics based on its proprietary bicyclic peptide (Bicycle) technology, reported financial results for the second quarter ended June 30, 2022 and provided recent corporate updates (Press release, Bicycle Therapeutics, AUG 4, 2022, View Source [SID1234617570]).

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"We are pleased with the progress of our wholly owned clinical oncology pipeline of Bicycle Toxin Conjugate, or BTC, programs and Bicycle tumor-targeted immune cell agonist, or Bicycle TICA, programs," said Kevin Lee, Ph.D., Chief Executive Officer of Bicycle Therapeutics. "In the second quarter, we initiated the expansion cohorts of our Phase I/II study of BT5528, and development of BT8009 and BT7480 remains on track as these programs advance in their respective clinical trials."

"In addition, we were delighted to announce the second expansion of our immuno-oncology collaboration with Genentech last month, highlighting the potential of the platform beyond our BTCs and Bicycle TICAs," Dr Lee continued. "We are pleased to have a strong balance sheet which helps support the advancement of our programs and which we anticipate provides a financial runway into 2025."

Second Quarter 2022 and Recent Highlights

Announced First Patient Dosed in the Expansion Cohorts of Phase I/II Trial of BT5528. In June 2022, Bicycle announced that the first patient was dosed in the expansion cohorts of the Phase I/II study of BT5528, Bicycle’s second-generation Bicycle Toxin Conjugate (BTC) targeting EphA2. Up to 56 patients will be enrolled in the initial expansion cohorts, with the ability to further expand enrollment based on the results from these cohorts. Bicycle intends to provide completed results of the dose escalation portion of the clinical trial during the third quarter of 2022.
Announced Expansion of Genentech Immuno-Oncology Collaboration. In July 2022, Bicycle announced that Genentech exercised an option to initiate a new program, expanding the exclusive strategic collaboration agreement with Bicycle to discover, develop and commercialize novel Bicycle-based immuno-oncology therapies. This expansion represented the second option exercised by Genentech under the terms of the original February 2020 agreement and triggered a $10 million payment to Bicycle, which is expected to be received in the third quarter of 2022.
Presented Trials in Progress Poster Featuring BT7480 Phase I/II Clinical Trial at the 2022 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting. In June 2022, Bicycle presented a Trials in Progress poster highlighting the Phase I/II clinical trial of BT7480, a novel, fully synthetic Bicycle TICA targeting Nectin-4 and agonizing CD137.
Announced Interim BT8009 Phase I Clinical Trial Results at the 2022 American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting. In April 2022, Bicycle announced interim Phase I results from the Phase I/II trial of BT8009, a second-generation BTC targeting Nectin-4. As of March 7, 2022, 37 patients have been dosed in the Phase I/II trial of BT8009. A total of 12 response evaluable urothelial cancer (UC) patients have been dosed in monotherapy cohorts of 2.5mg/m2 and 5.0mg/m2 weekly in the ongoing trial. Four response evaluable UC patients were dosed at 2.5mg/m2 weekly, with one patient observed to have tumor reductions constituting a confirmed partial response (PR) and two patients observed to have stable disease (SD). Eight response evaluable UC patients were dosed at 5.0mg/m2 weekly, with four patients observed to have a confirmed complete response (CR) or PR, including one patient with a CR and three patients with a PR, and two patients with SD, reflecting a 50% overall response rate and 75% disease control rate. As of March 7, 2022, the median duration of response had not yet been reached in either the 2.5 mg/m2 or 5.0mg/m2 cohort, with four of the five responders in these cohorts still on therapy after at least 24 weeks.
Exploration of additional doses and frequencies continues, and Bicycle intends to provide further updates this year.

Financial Results

Cash and cash equivalents were $372.8 million as of June 30, 2022, compared to $438.7 million as of December 31, 2021. The decrease in cash is primarily due to cash used in operating activities.
Research and development expenses were $19.9 million for the three months ended June 30, 2022, compared to $11.7 million for the three months ended June 30, 2021. The increase in expense of $8.2 million was primarily due to increased clinical program expenses for BT5528 and BT8009, Bicycle TICA program development expenses, as well as increased personnel-related expenses, including $1.6 million of incremental non-cash share-based compensation expenses, and increased facilities-related expenses.
General and administrative expenses were $11.8 million for the three months ended June 30, 2022, compared to $7.3 million for the three months ended June 30, 2021. The increase of $4.5 million for the three months ended June 30, 2022 as compared to the same period in the prior year was primarily due to an increase in personnel-related expenses, including $1.5 million of incremental non-cash share-based compensation expense, and an unfavorable effect of foreign exchange rates.
Net loss was $26.8 million, or $(0.90) basic and diluted net loss per share, for the three months ended June 30, 2022, compared to net loss of $17.9 million, or $(0.74) basic and diluted net loss per share, for the three months ended June 30, 2021.

On August 4, 2022 Mevion Medical Systems, the leading provider of compact proton therapy systems for use in radiation treatment for cancer patients, reported that the accelerator for the MEVION S250i Proton Therapy System was delivered on July 28, 2022, to Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology in Wuhan, China (Press release, Mevion Medical Systems, AUG 4, 2022, View Source [SID1234617602]). This milestone commences the system installation at Tongji Hospital’s proton therapy center, the first of its kind in Central China.

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The system at Tongji Hospital features Mevion’s industry leading HYPERSCAN Pencil Beam Scanning (PBS) technology and Adaptive Aperture pMLC. This powerful duo provides faster and more precise targeted dose delivery to tumors thus, minimizing the damage to surrounding healthy tissue and organs at risk. The system also integrates a diagnostic quality CT imaging system and a surface tracking system for high precision patient positioning and intra-fraction motion management.

Founded in 1900, Tongji Hospital currently treats over 6 million patients annually. It has developed into one of the world’s largest and most powerful oncology medical teaching and research facilities, and the recently opened Optics Valley Tongji Children’s Hospital is located on the same campus as the new proton therapy center. In addition to the Mevion system, the new proton therapy center will also be equipped with a cutting-edge whole-body PET/CT imaging system. Tongji Hospital has also built a second proton vault, making it China’s first proton center applying the One Plus One multi-system installation approach. This approach gives cancer centers the flexibility to add a second system in the future to correspond to the growth of patient volume and clinical expertise. By doing a staged installation approach, financial burdens are significantly reduced at the start of the clinical proton therapy program, and the risk of technology obsolescence is mitigated greatly.

"Mevion is excited to start the system installation at world-class Tongji Hospital, and we look forward to a continued partnership that will give patients in Central China much-needed access to proton therapy," said Tina Yu, Ph.D., chief executive officer and president of Mevion. "We are proud of our technology that provides advanced cancer treatment to patients and allows hospitals to expand their proton therapy program at their own pace."

*Mevion is actively seeking regulatory approval from the National Medical Products Administration (NMPA) in China.

On August 4, 2022 Compugen Ltd. (Nasdaq: CGEN), a clinical-stage cancer immunotherapy company and a pioneer in computational target discovery, reported that financial results for the second quarter ended June 30, 2022 (Press release, Compugen, AUG 4, 2022, View Source [SID1234617618]).

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Corporate Update

"Adapting to challenging market conditions, we have taken a strategic decision to focus on two prioritized indications, microsatellite stable-colorectal cancer (MSS-CRC) and non-small cell lung cancer (NSCLC), and wind down our broad Phase 1 cohort expansion program resulting in the conclusion of our collaboration with Bristol Myers Squibb," said Anat Cohen-Dayag, Ph.D., President, and Chief Executive Officer of Compugen. "I would like to thank Bristol Myers Squibb for our productive interactions and for their support in providing nivolumab and their anti-TIGIT, BMS-986207, enabling us to initiate the triple and dual combination studies to evaluate our DNAM-1 axis hypothesis at a time when our own differentiated anti-TIGIT, COM902 had not yet reached the clinic. Additionally, my sincere thanks to the investigators, their staff, and the patients for participating in these studies. This strategic decision allows us to extend our cash runway into the end of 2024, execute on our strong belief in COM701 and gives us the freedom to switch to and develop our own differentiated anti-TIGIT antibody, COM902. Concluding the collaboration with Bristol Myers Squibb provides us with what is expected to be the greatest opportunity to advance and partner our clinical assets and support a future path to registration."

Dr. Cohen-Dayag continued, "Our clinical data from the COM701/nivolumab dose escalation and cohort expansion study in a small number of MSS-CRC patients, show a modestly higher response rate compared to what has been reported for standard of care. We believe that this initial data, along with the translational package showing a COM701 driven mechanism, supports the evaluation of COM701 triple combination in a single arm study. The full data from the COM701/nivolumab cohort expansion study in MSS-CRC and details of the new study design along with timelines is expected to be presented once finalized in the fourth quarter of this year. The second indication we have prioritized is NSCLC in anti-PD-(L)1 treated patients. As an inflamed tumor type sensitive to PD-1 and possibly TIGIT checkpoints, NSCLC was selected as a tumor type with increased probability of responding to our triplet combination. We also plan to evaluate the blockade of PVRIG and TIGIT in combination with standard of care in this indication, to build an additional path to randomized studies. The design and timelines of the NSCLC program will be presented once finalized in the fourth quarter of this year. We believe focusing on these indications provides us with the highest probability of success, and we plan to share the progress and initial findings from these studies during 2023."

Dr. Cohen-Dayag added, "I am also extremely proud of the progress we have made in our preclinical portfolio. Several early-stage programs from our computational discovery platform are advancing in our pipeline with the most advanced program about to enter pre-IND enabling studies with first-in-class potential. We are very excited about this program, which is targeting a soluble immune checkpoint upregulated in the tumor microenvironment in response to IFN-γ. We developed a very high affinity antibody, COM503, to block this soluble immune checkpoint pathway and we believe we are the first to do so. The antibody has demonstrated preclinical in-vitro and in-vivo activity as monotherapy and in combination with other checkpoint inhibitors across various models and systems. We intend to share details on this program in the fourth quarter of this year."

Dr. Cohen-Dayag concluded, "With the decisive actions we have taken, we are being cash efficient and may be better positioned to bring value to our stakeholders. I am excited with what we have achieved and look forward to continuing to focus on execution and delivering value to our shareholders and patients."

Financial Results

As of June 30, 2022, cash, cash equivalents, short-term bank deposits and restricted cash totaled approximately $97 million, compared with approximately $118 million as of December 31, 2021. As a result of the Company’s strategic decision to end its Phase 1 program early and focus on two prioritized indications, the Company expects its existing cash and cash related balances to be sufficient to fund its operating plan into the end of 2024, without taking into consideration any cash inflows. Compugen does not have any debt.

R&D expenses for the second quarter ended June 30, 2022, were approximately $6.8 million, no change from the comparable period in 2021. Going into the second half of 2022, the reduction in R&D expenses is expected to be limited and will reflect winding down expenses of the current ongoing studies as well as preparation for the planned prioritized clinical studies. We expect that the full effect of the reduction in expenses will be reflected in 2023.

General and administrative expenses for the second quarter ended June 30, 2022, were approximately $2.6 million compared with approximately $2.7 million for the comparable period in 2021.

Cash balance at the end of 2022 is expected to be approximately $72-$74 million.

Net loss for the second quarter ended June 30, 2022, was approximately $9.1 million, or $0.11 per basic and diluted share, compared with a net loss of approximately $9.5 million, or $0.11 per basic and diluted share, in the comparable period of 2021.

Full financial tables are included below

Conference call and webcast information

The Company will hold a conference call today, August 4, 2022, at 8:30 AM ET to review its second quarter 2022 results. To access the live conference call by telephone, please dial 1-866-744-5399 from the U.S., or +972-3-918-0644 internationally. The call will be available via live webcast through Compugen’s website, located at the following link. Following the live audio webcast, a replay will be available on the Company’s website.

On August 4, 2022 Cytokinetics, Incorporated (Nasdaq: CYTK) reported financial results for the second quarter of 2022. Net loss for the second quarter was $19.8 million, or $0.23 per share, compared to net loss for the second quarter of 2021 of $61.6 million, or $0.86 per share (Press release, Cytokinetics, AUG 4, 2022, View Source,million%20at%20June%2030%2C%202022. [SID1234617702]). Cash, cash equivalents and investments totaled $596.7 million at June 30, 2022.

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In July, Cytokinetics raised $540 million netting approximately $383 million in proceeds through the offering of convertible senior notes, after deducting the purchasers’ discounts and commissions and Cytokinetics’ estimated offering expenses, as well as deducting $140.3 million to repurchase previously outstanding convertible senior notes. Cytokinetics expects to end 2022 with more than $800 million in cash.

"During the second quarter we made progress across regulatory, clinical and financial objectives. We engaged extensively with FDA in planning for its review of our NDA for omecamtiv mecarbil and advanced the enrollment and conduct of SEQUOIA-HCM and COURAGE-ALS while also planning for a second Phase 3 trial of aficamten," said Robert I Blum, Cytokinetics’ President and Chief Executive Officer. "We also bolstered our balance sheet by executing on a fundraising of over $500 million while reducing our planned nearer-term spending in 2022. We believe that we are in a strong position to bring our potential therapies to patients while also executing well on late-stage clinical development programs."

Q2 and Recent Highlights

Cardiac Muscle Programs

omecamtiv mecarbil (cardiac myosin activator)

Participated in a mid-cycle review meeting with the U.S. Food and Drug Administration (FDA) related to our New Drug Application (NDA) for omecamtiv mecarbil. Engaged extensively with FDA in other interactions related to its review of our NDA.

Received notice that the FDA plans to convene an Advisory Committee meeting to review the NDA for omecamtiv mecarbil, and that the meeting is currently scheduled for December 13, 2022.

Received notice that the FDA extended the Prescription Drug User Fee Act (PDUFA) date for omecamtiv mecarbil to February 28, 2023 due to additional pharmacokinetic analyses of omecamtiv mecarbil provided to the FDA upon request and that are deemed to constitute a major amendment to the NDA.

Hired and deployed Managed Healthcare Medical Scientists and initiated medical support of our global value, access and distribution services. Continued building headquarters-based commercial infrastructure and engaging in launch readiness activities, including pre-approval information exchange discussions with key payers. Conducted Business Process inventory for enterprise resource planning implementation and strategic sourcing activities to mitigate supply chain risks.

Presented additional data from GALACTIC-HF (Global Approach to Lowering Adverse Cardiac Outcomes Through Improving Contractility in Heart Failure) at Heart Failure 2022, an International Congress of the European Society of Cardiology, including:

An analysis showing that in patients with low blood pressure, there was a greater treatment effect from omecamtiv mecarbil on the primary composite endpoint of cardiovascular death or first heart failure event than in patients without low blood pressure such that there was an absolute risk reduction of 9.8 events per 100 patient-years (hazard ratio, 0.81; 95% confidence interval [CI] 0.70, 0.94; interaction p=0.051).

An analysis showing that the treatment effect of omecamtiv mecarbil on the primary composite endpoint was consistent across patients with no tricuspid regurgitation (TR), mild TR and moderate/severe TR such that baseline TR did not modify the treatment effect (interaction p=0.91).
Presented additional data from GALACTIC-HF at the American College of Cardiology 71st Annual Scientific Session (ACC.22) including:

An analysis showing that treatment with omecamtiv mecarbil in a subgroup of patients in GALACTIC-HF led to a reduction in resource intensity, with an estimated cost offset of $3,085, or a 19% reduction in costs per patient. The majority of cost reductions were due to heart failure hospitalizations avoided by patients treated with omecamtiv mecarbil.

An analysis showing that the effect of treatment with omecamtiv mecarbil was associated with similar risk reduction in the primary composite endpoint in both hospitalized patients and in outpatients, indicating that initiation of omecamtiv mecarbil was safe and well tolerated in both hospitalized patients and outpatients.
Announced results of METEORIC-HF (Multicenter Exercise Tolerance Evaluation of Omecamtiv Mecarbil Related to Increased Contractility in Heart Failure), a Phase 3 clinical trial of omecamtiv mecarbil in patients with HFrEF that evaluated the effect of treatment with omecamtiv mecarbil compared to placebo on exercise capacity as determined by cardiopulmonary exercise testing (CPET). After 20 weeks of treatment, there was no change in peak oxygen uptake (pVO2) in patients treated with omecamtiv mecarbil versus placebo. Adverse events, including major cardiac events, were similar between the treatment arms, and the safety profile of omecamtiv mecarbil was consistent with prior clinical trials, including GALACTIC-HF.

Published a manuscript entitled "Effects of Omecamtiv Mecarbil in Heart Failure with Reduced Ejection Fraction According to Blood Pressure: The GALACTIC-HF Trial" in the European Heart Journal.

Published a manuscript entitled "The Effect of Omecamtiv Mecarbil on Exercise Capacity in Chronic Heart Failure with Reduced Ejection Fraction: The METEORIC-HF Randomized Trial" in the Journal of the American Medical Association.

aficamten (cardiac myosin inhibitor)

Presented the first long-term data from REDWOOD-HCM OLE (Randomized Evaluation of Dosing With CK-274 in Obstructive Outflow Disease in HCM Open Label Extension) at Heart Failure 2022 from 38 patients treated for up to 24 weeks showing that treatment with aficamten was associated with substantial reductions in the average resting left ventricular outflow tract gradient (LVOT-G) and Valsalva LVOT-G. The reductions started to occur within two weeks of treatment, were sustained through 24 weeks of treatment, and were achieved with only modest decreases in the average LVEF. Improvements were also observed in New York Heart Association (NYHA) Functional Class and cardiac biomarkers including NTpro-BNP and cardiac troponin. Treatment with aficamten was well-tolerated with one temporary discontinuation due to LVEF <50% and one temporary down-titration, neither related to drug. Both patients remain on treatment with aficamten.

Presented additional data from REDWOOD-HCM at the American Society of Echocardiography (ASE) 33rd Annual Scientific Sessions showing that measures of cardiac structure, diastolic and mitral valve function improved in patients treated with aficamten after 10 weeks, including a significant reduction in left atrial volume index (p<0.01) and a trend towards a reduction in left ventricular hypertrophy (left ventricular mass index; p=0.06). Treatment with aficamten also resulted in improved ventricular relaxation and filling, as indicated by a reduction in lateral E/e’ (p<0.01) and an increase in lateral e’ (p<0.05).

Announced positive data from Cohort 3 of REDWOOD-HCM, which enrolled patients with symptomatic obstructive hypertrophic cardiomyopathy (HCM) and a resting left LVOT-G ≥50, or resting LVOT-G ≥30 mmHg and post-Valsalva LVOT-G ≥50 mmHg, whose background therapy included disopyramide and in the majority a beta-adrenergic blocker. Results showed that substantial reductions in the average resting LVOT-G as well as the post-Valsalva LVOT-G (defined as resting gradient <30 mmHg and post-Valsalva gradient <50 mmHg) were achieved. The safety and tolerability of aficamten were consistent with prior experience in REDWOOD-HCM with no treatment interruptions and no serious adverse events attributed to treatment reported by the investigators.

Began developing the go-to-market strategy for aficamten to support its potential future commercialization.

Published a manuscript entitled "Characteristics of Patients with Obstructive Hypertrophic Cardiomyopathy in Real-World Community-Based Cardiovascular Practices" in The American Journal of Cardiology.

Skeletal Muscle Program

reldesemtiv (fast skeletal muscle troponin activator (FSTA))

Continued conduct and enrollment of COURAGE-ALS (Clinical Outcomes Using Reldesemtiv on ALSFRS-R in a Global Evaluation in ALS), the Phase 3 clinical trial of reldesemtiv in patients with amyotrophic lateral sclerosis (ALS).

Started COURAGE-ALS OLE (Clinical Outcomes Using Reldesemtiv on ALSFRS-R in a Global Evaluation in ALS Open Label Extension), an open-label extension clinical study designed to assess the long-term safety and tolerability of reldesemtiv in people with ALS who have previously participated in COURAGE-ALS.

Pre-Clinical Development and Ongoing Research

Continued to advance new muscle directed compounds and conduct IND-enabling studies with the expectation of our potentially moving 1-2 drug candidates into clinical development in the next year.

Continued research activities directed to our other muscle biology research programs.

Corporate

Raised $523.3 million in net proceeds, after deducting underwriters’ discounts and transaction fees, and before repurchasing previously outstanding 2026 convertible senior notes.

Announced changes to the Board of Directors including the retirement of L. Patrick Gage, Ph.D., former Chairman of the Board, the appointment of John T. Henderson, M.B., Ch.B. as the company’s new Chairman, and the appointment of Robert A. Harrington, M.D., Arthur L. Bloomfield Professor and Chair, Department of Medicine, Stanford University, to the Board.

Announced the continuation of our partnership with The ALS Association in the fight against ALS.

Upcoming Corporate Milestones

Cardiac Muscle Programs

omecamtiv mecarbil (cardiac myosin activator)

Participate in Advisory Committee meeting to review the NDA for omecamtiv mecarbil on December 13, 2022.

Launch omecamtiv mecarbil in the U.S. subject to FDA approval in Q1 2023.

aficamten (cardiac myosin inhibitor)

Continue enrolling patients with obstructive HCM in SEQUOIA-HCM through 2022 with results expected in 2H 2023.

Continue enrolling patients with non-obstructive HCM in Cohort 4 of REDWOOD-HCM with results expected in 1H 2023.

Begin second Phase 3 clinical trial of aficamten in obstructive HCM in Q4 2022.

Expect to share additional data from the open label extension study of aficamten, REDWOOD-HCM OLE in 2H 2022.

CK-3828136 (CK-136) (cardiac troponin activator)

Reactivate development program for CK-136 in 2H 2022.

Skeletal Muscle Program

reldesemtiv (fast skeletal muscle troponin activator (FSTA))

Expect the Data Monitoring committee to conduct the first interim analysis (assessing for futility) from COURAGE-ALS in Q4 2022.

Financials

Revenues for the three and six months ended June 30, 2022 were $89.0 million and $90.1 million, respectively, compared to $2.8 million and $9.4 million for the corresponding period in 2021. The increase in revenues was primarily due to the recognition of $87.0 million of deferred revenue for royalties on the net sales of products containing mavacamten as a result of the extinguishment of royalty obligations.

Research and development expenses for the three and six months ended June 30, 2022 increased to $57.1 million and $103.1 million, respectively, compared to $36.4 million and $68.0 million for the same period in 2021. The changes were primarily due to increases in spending for clinical development activities for COURAGE-ALS, for our cardiac muscle inhibitor programs, and early research programs.

General and administrative expenses for the three and six months ended June 30, 2022 increased to $42.7 million and $75.8 million, respectively, from $21.2 million and $36.8 for the same period in 2021 due primarily to higher outside services spending in anticipation of the potential commercial launch of omecamtiv mecarbil, and an increase in personnel related costs including stock-based compensation.

Revised 2022 Financial Guidance

The company today revised its financial guidance related to a reduction in expected operating expenses as a result of the three-month extension of the PDUFA date for omecamtiv mecarbil to February 28, 2023, which shifted certain hiring and activities previously planned to occur in 2022 to 2023. The company anticipates operating expenses for 2022 will be in the range of $375 to $385 million, and net cash utilization will be approximately $360 to $365 million. The company expects to end 2022 with more than $800 million, representing between two and three years of forward cash.

Conference Call and Webcast Information

The conference call will be simultaneously webcast and can be accessed from the homepage and in the Investors & Media section of Cytokinetics’ website at www.cytokinetics.com. The live audio of the conference call can also be accessed by telephone by registering in advance at the following link: Cytokinetics Q2 2022 Earnings Conference Call. Upon registration, participants will receive a dial-in number and a unique passcode to access the call. An archived replay of the webcast will be available via Cytokinetics’ website for twelve months.

On August 4, 2022 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, 2022 (Press release, Karyopharm, AUG 4, 2022, View Source [SID1234617454]).

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"I’m pleased with our team’s ongoing commitment to successfully execute against key priorities in the second quarter, achieving more than 75% year-over-year revenue growth and further expanding patient access for selinexor globally following full marketing authorization from the European Commission and recent launches in China and Canada," said Richard Paulson, President and Chief Executive Officer of Karyopharm. "Despite headwinds caused by COVID-19 at the beginning of the year and increased competition for later lines of multiple myeloma treatment, we continue to see increased use of XPOVIO in earlier lines with growth in the community setting. Looking ahead to the remainder of the year, we have several key upcoming milestones, including reporting additional data from our studies of selinexor in front-line myelofibrosis and eltanexor in relapsing/refractory myelodysplastic syndromes."

Second Quarter 2022 and Recent Highlights

XPOVIO Commercial Performance

Achieved U.S. net product revenue for the second quarter of 2022 of $29.0 million, a 44% increase compared to the second quarter of 2021, driven by strong year-over-year growth in new patient starts and refills, with continued shift of XPOVIO into second to fourth lines of therapy.

In the second quarter of 2022, a recovery in new patient starts as compared to the previous quarter was offset by the decline in refills due to COVID-19 related reduction of new patient starts in the beginning of the year and intensified late-line competition in the academic setting.

XPOVIO continued its growth in the community setting, driven by a positive shift in perception and intent to treat metrics.

Increased selinexor’s reach to patients around the world with the full marketing authorization of NEXPOVIO (selinexor) in Europe, which expands the indication in multiple myeloma to patients with multiple myeloma after at least one prior therapy as well as commercial launches in mainland China and Canada by partners Antengene Corporation Limited and FORUS Therapeutics Inc., respectively.
Research & Development (R&D) Highlights for Selinexor and Eltanexor

European Commission granted marketing authorization of NEXPOVIO in combination with once weekly bortezomib (Velcade) and low-dose dexamethasone (XVd) for the treatment of adults with multiple myeloma who have received at least one prior therapy, expanding on the prior approval which was in combination with dexamethasone for the treatment of multiple myeloma in adult patients who have received at least four prior therapies and whose disease is refractory to at least two proteasome inhibitors, two immunomodulatory agents and an anti-CD38 monoclonal antibody, and who have demonstrated disease progression on the last therapy.

Results from Phase 1/2 study of selinexor in combination with ruxolitinib in treatment-naïve myelofibrosis were presented at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) 2022 Annual Meeting, including a generally manageable side effect profile with no dose limiting toxicities and 75% of evaluable patients demonstrating ≥35% spleen volume reduction (SVR 35) at week 12. The most commonly reported Grade 3/4 treatment emergent adverse events were thrombocytopenia (27%), anemia (20%) and neutropenia (20%). These data were also presented at the European Hematology Association (EHA) (Free EHA Whitepaper) 2022 Hybrid Congress.

Following productive discussions with the U.S. Food and Drug Administration (FDA), the Company is finalizing a partner for a companion diagnostic to be used in a registration-enabling study of selinexor in patients with p53 wild-type endometrial cancer.

FDA granted fast track designation for the development program of eltanexor as monotherapy for the treatment of patients with relapsed or refractory intermediate, high-, or very high-risk myelodysplastic syndromes (MDS), per IPSS-R. In addition, the FDA also granted eltanexor orphan drug designation for the treatment of MDS and selinexor for the treatment of myelofibrosis.

The European Commission granted EU orphan medicinal product designation for eltanexor for the treatment of MDS.
2022 Financial Guidance

Based on its current operating plans, Karyopharm is updating its guidance for full year 2022:

Total revenue to be in the range of $155 million to $165 million.

XPOVIO net product revenue to be in the range of $120 million to $130 million versus previous guidance of $135 million to $145 million.

Non-GAAP R&D and Selling, general and administrative (SG&A) expenses, excluding stock-based compensation expense, to be in the range of $250 million to $265 million versus previous guidance of $265 million to $280 million.

Karyopharm has not reconciled the full year 2022 outlook for non-GAAP R&D and SG&A expenses to full year 2022 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 2022 outlook for non-GAAP R&D and SG&A expenses.

The Company continues to expect that its existing cash, cash equivalents and investments, and 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 early 2024.
Second Quarter 2022 Financial Results

Total Revenues: Total revenue for the second quarter of 2022 was $39.7 million, up 76% compared to $22.6 million for the second quarter of 2021.

Net product revenue: Net product revenue for the second quarter of 2022 was $29.0 million, up 44% compared to $20.2 million for the second quarter of 2021.

License and other revenue: License and other revenue for the second quarter of 2022 was $10.7 million, compared to $2.4 million for the second quarter of 2021. The increase was primarily attributable to $6.5 million earned in reimbursement of development expenses from the Menarini Group.

Cost of sales: Cost of sales for the second quarter of 2022 were $0.9 million, compared to $1.1 million for the second quarter of 2021. Cost of sales reflects the costs of XPOVIO units sold and third-party royalties on net product revenue.

R&D expenses: R&D expenses for the second quarter of 2022 were $44.3 million, compared to $34.0 million for the second quarter of 2021. The increase was primarily driven by an increase in personnel costs and stock-based compensation, including $3.8 million of severance-related stock-based compensation expense incurred during the three months ended June 30, 2022.

SG&A expenses: SG&A expenses for the second quarter of 2022 were $37.3 million, compared to $36.5 million for the second quarter of 2021. The increase in SG&A expenses was primarily due to an increase in stock-based compensation as a result of $3.5 million of severance-related stock-based compensation expense incurred during the three months ended June 30, 2022.

Interest expense: Interest expense for the second quarter of 2022 was $6.3 million, compared to $5.0 million for the second quarter of 2021.

Net loss: Karyopharm reported a net loss of $49.1 million, or $0.62 per share, for the second quarter of 2022, compared to a net loss of $53.6 million, or $0.71 per share, for the second quarter of 2021. Net loss included non-cash stock-based compensation expense of $15.1 million and $8.1 million for the second quarters of 2022 and 2021, respectively.

Cash position: Cash, cash equivalents, restricted cash and investments as of June 30, 2022, totaled $172.6 million, compared to $235.6 million as of December 31, 2021.

Non-GAAP Financial Information

Karyopharm uses a non-GAAP financial measure, non-GAAP 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, August 4, 2022, at 8:00 a.m. Eastern Time, to discuss the second quarter 2022 financial results and provide other business highlights. To access the conference call, please dial (888) 349-0102 (local) or (412) 902-4299 (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, along with accompanying slides, 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 exportin 1 (XPO1) inhibitor and the first of Karyopharm’s Selective Inhibitor of Nuclear Export (SINE) compounds to be approved for the treatment of cancer. XPOVIO functions by selectively binding to and inhibiting the nuclear export protein XPO1. XPOVIO is approved in the U.S. and marketed by Karyopharm in multiple oncology indications, including: (i) in combination with Velcade (bortezomib) and dexamethasone (XVd) in patients with multiple myeloma after at least one prior therapy; (ii) in combination with dexamethasone in patients with heavily pre-treated multiple myeloma; and (iii) in patients with diffuse large B-cell lymphoma (DLBCL), including DLBCL arising from follicular lymphoma, after at least two lines of systemic therapy. XPOVIO (also known as NEXPOVIO in certain countries) has received regulatory approvals in various indications in a growing number of ex-U.S. territories and countries, including but not limited to the European Union, the United Kingdom, China, South Korea, Canada and Israel, and is marketed in those areas by Karyopharm’s global partners.

Please refer to the local Prescribing Information for full details.

Selinexor is also being investigated in several other mid- and late-stage clinical trials across multiple high unmet need cancer indications, including in endometrial cancer and myelofibrosis.

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]

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.