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 Biodesix, Inc. (Nasdaq: BDSX), a leading data-driven diagnostic solutions company with a focus in lung disease, reported its financial and operating results for second quarter ended June 30, 2022 and provided a corporate update (Press release, Biodesix, AUG 4, 2022, View Source [SID1234617569]).

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"We are thrilled to announce strong growth from our core lung diagnostic testing, with an increase in revenue of 52% over the second quarter of 2021 and 56% over the first quarter of 2022," said Scott Hutton, CEO of Biodesix. "With the recent Medicare coverage of the Nodify CDT test, all five of our core lung diagnostic tests are now covered, which will help drive adoption of the test and improve margins over the long term.

In addition, we announced two exciting corporate arrangements. The first, announced with Royal Phillips, integrates our Nodify Lung tests into its Lung Cancer Orchestrator patient management system to help facilitate digital ordering of the tests following detection of a lung nodule with the ultimate goal of improving patient care and outcomes. The second, announced with Memorial Sloan Kettering Cancer Center and Bio-Rad Laboratories, allows us to leverage the capabilities of these leading organizations to potentially bring new transformative diagnostics to market, including our initial intention to co-develop a molecular minimal residual disease (MRD) test for solid tumors.

Overall, our progress and positive trends in our core lung diagnostics tests in the first half of the year solidifies our confidence in reaffirming our 2022 revenue guidance."

Second Quarter 2022 Financial Results

For the three-month period ended June 30, 2022, as compared to the same period of 2021 (where applicable):

Total revenue of $11.0 million, a decrease of 8%, driven primarily by an anticipated year-over-year decline in COVID-19 diagnostic testing revenue, offset by strong year-over-year growth in core lung diagnostics:
Core lung diagnostic revenue of $7.3 million, reflected a year-over-year increase of 52% that was driven primarily by the increased adoption of Nodify Lung nodule management tests (Nodify CDT & Nodify XL2 tests);
COVID-19 testing revenue of $3.0 million reflected a year-over-year decrease of 51% that was driven by the shift to at-home rapid antigen testing;
BioPharma Services revenue of $0.7 million decreased 29% year-over-year. COVID-related delays in clinical study enrollment and sample shipping logistics have begun to recover but are still impacting timelines for existing and new agreements;
Second quarter 2022 gross margin of $7.0 million, or 64% as a percentage of revenue as compared to 40% in the comparable prior year period primarily driven by the shift of sales to higher-margin core lung diagnostics and away from lower-margin COVID-19 testing;
Operating expenses (excluding direct costs and expenses) of $18.6 million, an increase of 21% driven primarily by growth in sales and marketing to drive our growth in core lung diagnostics sales as well as the recent GeneStrat NGS commercial launch;
Includes non-cash stock compensation expense of $1.4 million as compared to $0.5 million;
Net loss of $15.8 million, an increase of 39%, driven primarily by the loss on extinguishment charge resulting from the restructuring of the contingent consideration agreement with Integrated Diagnostics (Indi);
Cash and cash equivalents of $28.7 million, inclusive of $5.1 million in restricted cash, as of June 30;
Raised net proceeds of $27.3 million during the quarter through debt and equity offerings;
Includes principal payment of $3.0 million on the 2021 Term Loan and $2.0 million for scheduled milestone payment in April 2022 to Indi.
2022 Financial Outlook

The Company reaffirms its 2022 financial outlook and expects to generate between $37.5 million and $39.5 million in total revenue in 2022.

An archived replay of the webcast will be available on the Company’s website for a period of 90 days.

For a full list of Biodesix’s press releases and webinars, please visit Biodesix.com.

On August 4, 2022 Day One Biopharmaceuticals (Nasdaq: DAWN), a clinical-stage biopharmaceutical company dedicated to developing and commercializing targeted therapies for people of all ages with life-threatening diseases, reported financial results for the second quarter of 2022 and highlighted recent corporate achievements (Press release, Day One, AUG 4, 2022, View Source [SID1234617568]).

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"Day One continues to deliver on our mission. During this past quarter we announced positive initial data from the ongoing pivotal FIREFLY-1 study with tovorafenib in relapsed pLGG and raised $172.5 million in a follow-on public offering, which will fund the company into 2025," said Jeremy Bender, Ph.D., chief executive officer of Day One. "We look forward to the topline results from the full FIREFLY-1 pivotal study population in the first quarter of 2023. We are also excited to have recently expanded the development of tovorafenib into newly-diagnosed pLGG patients (FIREFLY-2/LOGGIC), and we continue to enroll patients in our Phase 2 FIRELIGHT-1 trial evaluating tovorafenib both as a monotherapy and in combination with pimasertib in adolescent and adult patients with solid tumors harboring MAPK alterations."

Program Highlights

Announced positive initial data from the pivotal FIREFLY-1 trial of tovorafenib in relapsed pLGG. Initial data from the first 25 patients enrolled in the trial showed:
64% overall response rate (ORR) and 91% CBR (partial response/unconfirmed partial response + stable disease) in the 22 RANO-evaluable patients
14 partial responses (13 confirmed responses and 1 unconfirmed response)
6 patients with stable disease
All patients with stable disease (n=6) were noted to have tumor shrinkage, ranging between 19% and 43%
Responses were observed in patients with both BRAF fusions and BRAF V600E mutations who received prior MAPK-targeted therapy
The median-time-to-response was 2.8 months
A heavily-pretreated population, with a median of 3 prior lines of therapy (range: 1-9)
All patients who responded remain on therapy (n=14) and no patients have discontinued treatment due to treatment-related adverse events
Initial safety data indicated monotherapy tovorafenib to be generally well-tolerated
The majority of adverse events (AEs) were grade 1 or 2 in nature; the most common (≥25% any grade) treatment related AEs were increase in blood creatine phosphokinase, rash, and hair color changes
Treatment-related AEs of grade 3 or greater occurred in nine patients (36%)

Day One has initiated a pivotal Phase 3 clinical trial (FIREFLY-2/LOGGIC) evaluating tovorafenib as a front-line therapy for patients newly diagnosed with pLGG.
The study is a randomized, monotherapy, open-label trial aiming to enroll approximately 400 patients aged 6 months to 25 years across approximately 100 sites globally, including in the United States, Europe and Asia
The primary endpoint will be the ORR based upon RANO criteria as reported by Blinded Independent Central Review
Secondary endpoints will include safety, progression-free survival, overall survival, duration of response, functional outcomes and quality of life measures

Day One continues to enroll patients in the Phase 2 FIRELIGHT-1 trial evaluating tovorafenib as a monotherapy and as a combination with the company’s MEK inhibitor, pimasertib, in adults and adolescents with recurrent, progressive, or refractory solid tumors harboring MAPK pathway aberrations.
Corporate Highlights and Upcoming Milestones

In June 2022, Day One announced the successful closing of an upsized public offering, raising gross proceeds of $172.5 million, which extends the Company’s cash runway into 2025.
Day One anticipates releasing topline results for the full FIREFLY-1 pivotal study population in the first quarter of 2023. If the data are supportive, Day One expects to submit a new drug application (NDA) to the United States Food and Drug Administration (FDA) in the first half of 2023.
Day One expects to dose the first patient in FIREFLY-2/LOGGIC trial in the third quarter of 2022.
Second Quarter 2022 Financial Highlights

Cash Position: Cash, cash equivalents and short-term investments totaled $394.9 million on June 30, 2022. Based on Day One’s current operating plan, management believes it has sufficient capital resources to fund anticipated operations into 2025.

R&D Expenses: Research and development expenses were $22.6 million for the second quarter of 2022 compared to $9.9 million for the second quarter of 2021. The increase was primarily due to additional employee compensation costs, clinical trial and pre-commercial manufacturing activities related to Day One’s lead product candidate, tovorafenib.

G&A Expenses: General and administrative expenses were $14.2 million for the second quarter of 2022 compared to $5.5 million for the second quarter of 2021. The increase was primarily due to additional employee compensation costs, initial commercial buildout, and professional service expenses to support company growth.

Net Loss: Net loss totaled $36.5 million for the second quarter of 2022 compared to $15.5 million for the second quarter of 2021 with non-cash stock compensation expense of $5.6 million and $2.5 million for the second quarters of 2022 and 2021, respectively.
Upcoming Events

2022 Wedbush PacGrow Healthcare Virtual Conference
Management will participate in a panel discussion on Tuesday, August 9, 2022 at 10:55 a.m. ET. A live and archived audio webcast of the discussion will be available for 30 days by visiting the Events & Presentations section of the Company’s website.
Morgan Stanley 20th Annual Global Healthcare Conference, September 12-14, 2022
About Tovorafenib
Tovorafenib is an investigational, oral, brain-penetrant, highly selective type II pan-RAF kinase inhibitor designed to target a key enzyme in the MAPK signaling pathway, which is being investigated in primary brain tumors and solid tumors harboring activating RAF alterations. Tovorafenib has been studied in over 325 patients to date. Currently tovorafenib is under evaluation in a pivotal Phase 2 clinical trial (FIREFLY-1) among pediatric, adolescent and young adult patients with relapsed pediatric low-grade glioma (pLGG), which is an area of considerable unmet need with no approved therapies for the majority of patients. Day One has also initiated a pivotal Phase 3 study (FIREFLY-2/LOGGIC) in newly-diagnosed patients with pLGG. Beyond pLGG, tovorafenib is being evaluated alone or as a combination therapy for adolescent and adult patient populations with recurrent or progressive solid tumors with MAPK pathway aberrations (FIRELIGHT-1). Tovorafenib has been granted Breakthrough Therapy and Rare Pediatric Disease designations by the U.S. Food and Drug Administration (FDA) for the treatment of patients with pLGG harboring an activating RAF alteration. Tovorafenib has also received Orphan Drug designation from the FDA for the treatment of malignant glioma, and from the European Commission (EC) for the treatment of glioma.

About Pimasertib
Pimasertib is an investigational, oral, highly selective, small molecule inhibitor of mitogen‐activated protein kinases 1 and 2 (MEK-1/-2) within the MAPK signaling pathway. Pimasertib has been dosed in over 850 patients to date for various tumor types. Preclinical data indicates that the combination of a MEK inhibitor, such as pimasertib, and a type II RAF inhibitor, such as tovorafenib, has synergistic anti-tumor activity.

Day One is conducting a Phase 1b/2 study (FIRELIGHT-1) to evaluate the safety, tolerability, and preliminary efficacy of combining pimasertib with tovorafenib in adolescent and adult patients (≥12 years of age) with recurrent, progressive, or refractory solid tumors with MAPK pathway aberrations.

On August 4, 2022 Yumanity Therapeutics, Inc. ("Yumanity" or the "Company") (Nasdaq: YMTX), a clinical-stage biopharmaceutical company focused on the discovery and development of innovative, disease-modifying therapies for neurodegenerative diseases, reported financial results for the second quarter ended June 30, 2022, and provided an overview of the Company’s recent corporate developments (Press release, Yumanity Therapeutics, AUG 4, 2022, View Source [SID1234617567]).

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Recent Corporate Developments

In June 2022, the Company announced definitive agreements for two strategic transactions. The first definitive agreement is an asset purchase agreement for the sale of Yumanity’s lead clinical-stage product candidate, YTX-7739, as well as Yumanity’s unpartnered discovery-stage neuroscience product candidates and targets to Janssen Pharmaceutica NV ("Janssen"), part of the Janssen Pharmaceutical Companies of Johnson & Johnson, for $26 million in cash. Under the second definitive agreement, Kineta, Inc., ("Kineta") will become a wholly-owned subsidiary of Yumanity in an all-stock transaction, resulting in a combined publicly traded company re-named Kineta, Inc., that will focus on immuno-oncology and continue Yumanity’s ongoing research collaboration with Merck & Co. in amyotrophic lateral sclerosis and frontotemporal lobar dementia. The two transactions are expected to close in the second half of 2022, subject to customary closing conditions, including approval of both transactions by the stockholders of Yumanity.
Second Quarter 2022 Financial Highlights

Cash position: As of June 30, 2022, cash, cash equivalents and investments were $11.8 million, compared to $36.5 million as of December 31, 2021. The decrease was primarily due to a $12.8 million payment to extinguish the Company’s remaining debt during the first quarter of 2022, spending on the clinical development of YTX-7739 primarily in the first quarter of 2022, and costs related to being a public company. As of the issuance date of the condensed consolidated financial statements for the period ended June 30, 2022, the Company expects that, absent either strategic transaction, its cash, cash equivalents and marketable securities will be sufficient to fund its operating expenses early into the first quarter of 2023.

Research and development (R&D) expense: Research and development expense was $1.1 million compared to $7.3 million for the second quarter of 2021. The decrease in R&D expense was primarily due to the elimination of a significant portion of the Company’s R&D personnel in connection with the restructuring announced in February 2022 as well as pausing of clinical development efforts for YTX-7739 while the FDA partial clinical hold is in effect.

General and administrative expense: General and administrative expense was $5.6 million compared to $4.7 million for the second quarter of 2021. The increase was primarily attributable to higher legal fees and investment banking fees incurred in connection with the transactions contemplated by the merger agreement with Kineta and the asset purchase agreement with Janssen.

Net loss: The Company reported a net loss of $4.8 million, or $0.45 per basic and diluted share, compared to a net loss of $10.5 million, or $1.03 per basic and diluted share for the second quarter of 2021. The decrease in net loss was due primarily to the decrease in R&D expense as described above. The Company expects to continue to generate operating losses for the foreseeable future, although at reduced expected levels as a result of restructuring actions taken in the six months ended June 30, 2022.

On August 4, 2022 Marker Therapeutics, Inc. (Nasdaq: MRKR), a clinical-stage immuno-oncology company specializing in the development of next-generation T cell-based immunotherapies for the treatment of hematological malignancies and solid tumor indications, reported that the U.S. Food and Drug Administration (FDA) has cleared the Company’s Investigational New Drug (IND) application for MT-601, a multi-tumor-associated antigen (multiTAA)-specific T cell product targeting six antigens, for the treatment of patients with relapsed/refractory non-Hodgkin lymphoma who have failed or are ineligible to receive anti-CD19 CAR T cell treatment (Press release, Marker Therapeutics, AUG 4, 2022, View Source [SID1234617566]).

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"This new clinical trial will build upon results that were observed in the Phase I/II TACTAL study conducted by BCM, which assessed the safety and efficacy of five-antigen-directed multiTAA-specific T cell product," stated Dr. Mythili Koneru, Marker’s Chief Medical Officer. "In the TACTAL study, BCM observed long-term CR rates that were comparable to recently approved CD19 CAR-T therapies, even at very low cell doses. Unlike CD19 CAR-T cell therapies, patients receiving multiTAA-specific T cell product had superior durability of response, without the severe toxicities that commonly occur with other adoptive cell therapies, such as cytokine release syndrome or neurotoxicity. Based on these results, we believe that multiTAA-specific T cell products can be easily administered in an outpatient setting without hospitalization."

In the TACTAL study, patients were treated with five-antigen-directed multiTAA-T cell product. Based upon the safety profile observed with multiTAA-specific T cell therapies containing WT-1 in multiple cancer indications, the FDA cleared in the IND the addition of WT-1 as the sixth tumor-associated antigen to the MT-601 product that will be used to treat patients in the Marker sponsored study. In addition, the FDA has cleared Marker to initiate its study at a dose level of 200 million cells per infusion, versus the dose range of 10-40 million cells per infusion used in the TACTAL study. This increase in the cell dose will be possible due to Marker’s development and adoption of a 9-day manufacturing process, which also accelerates the time to treatment.

Dr. Koneru continued: "We believe that the most important finding of the TACTAL study was that the administration of multiTAA therapy consistently drove an enhanced immunological response from the patient’s own immune system, which we believe was due to the lack of lymphodepletion which allowed the patient’s own immune system to play a part. We believe that this phenomenon, known as epitope spreading, was critical in driving more durable responses than have been observed with other cell therapies like TCRs and CAR-Ts. It is notable that none of the patients who developed a CR in the TACTAL study relapsed during the follow up period, and several patients have been in CR for over five years at their last follow-up. This contrasts strongly with the experience of CD-19 CAR-Ts, where up to 40% of patients are expected to relapse within 12 months of developing a complete response."

Marker’s MT-601 Phase 1 trial will focus on r/r NHL patients who have failed CD19 CAR-T therapy, or those who are ineligible for treatment with those therapies. MT-601 targets a series of tumor antigens other than CD19, offering patients a therapeutic alternative even if their tumor has escaped by downregulating the expression of CD19. For patients who cannot access CD19 therapies, MT-601 has the potential to generate objective responses, with tolerability and potentially longer duration of response.

"FDA clearance of our IND for MT-601 is a significant milestone as we advance our pipeline in a number of Company-sponsored trials," said Peter L. Hoang, Marker’s President and Chief Executive Officer. "We believe that MT-601, which targets six tumor-associated antigens highly expressed in lymphoma, has the potential to build upon results of the TACTAL study. We look forward to initiating our Company-sponsored Phase 1 study next year."