On August 3, 2023 Curis, Inc. (NASDAQ: CRIS), a biotechnology company focused on the development of emavusertib, an orally available, small molecule IRAK4 inhibitor for the treatment of hematologic malignancies, reported its business update and financial results for the second quarter ended June 30, 2023 (Press release, Curis, AUG 3, 2023, View Source [SID1234633742]).

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"We are very pleased with our progress this quarter, as we were able to work with the FDA to remove the partial clinical hold on the TakeAim Leukemia study a quarter ahead of schedule. In that process, we also gained alignment with FDA in confirming 300 mg BID as the RP2D for monotherapy, which we believe is the optimal monotherapy dose. We appreciate the strong support of our clinical investigators during our discussions with FDA and we are excited to expand patient enrollment in the TakeAim Leukemia study at the RP2D," said James Dentzer, President and CEO of Curis.

Second Quarter 2023 and Recent Operational Highlights

Precision Oncology, Emavusertib (IRAK4 Inhibitor)

TakeAim Leukemia

In July, the Company announced that the U.S. Food and Drug Administration (FDA) removed the partial clinical hold on the TakeAim Leukemia Phase 1/2 study of emavusertib. Further, the recommended phase 2 dose (RP2D) for emavusertib as a monotherapy has been confirmed at 300 mg BID in patients with Acute Myelogenous Leukemia (AML) or Myelodysplastic Syndromes (MDS).
The Company is currently enrolling relapsed or refractory (R/R) AML patients with FLT3 mutation or a spliceosome mutation (U2AF1 or SF3B1 mutation) who have received ≤ 2 prior lines of treatment in the monotherapy study.
The Company is also planning a combination study of emavusertib with azacitidine and venetoclax to treat AML patients in the front-line setting.
TakeAim Lymphoma

The Company is focusing its lymphoma clinical development efforts on Primary CNS lymphoma (PCNSL), a rare form of extranodal non-Hodgkin lymphoma for which there are limited treatment options. The Company is currently enrolling pCNSL patients in its TakeAim Lymphoma study in which patients are being treated with a combination of emavusertib and ibrutinib.
Upcoming Milestones

We expect updated clinical data in both the monotherapy and combination studies in 2024.
Corporate

In July 2023, the Company completed a registered direct offering with net proceeds of approximately $13.8 million.

First Quarter 2023 Financial Results

For the second quarter of 2023, Curis reported a net loss of $12.0 million or $0.12 per share on both a basic and diluted basis as compared to $15.9 million or $0.17 per share on both a basic and diluted basis, for the same period in 2022. Curis reported a net loss of $23.5 million or $0.24 per share on both a basic and diluted basis, for the six months ended June 30, 2023 as compared to a net loss of $32.0 million or $0.35 per share on both a basic and diluted basis for the same period in 2022.

Revenues for the first quarter of 2023 were $2.2 million as compared to $2.4 million for the same period in 2022. Revenues for both periods consist of royalty revenues from Genentech’s and Roche’s sales of Erivedge. Revenues for the six months ended June 30, 2023 and 2022 were both $4.5 million.

Research and development expenses were $10.0 million for the second quarter of 2023, as compared to $12.3 million for the same period in 2022. The decrease was primarily attributable to lower employee related costs due to a reduction in headcount. Research and development expenses were $19.2 million for the six months ended June 30, 2023, as compared to $23.8 million for the same period in 2022.

General and administrative expenses were $4.2 million for the second quarter of 2023, as compared to $5.1 million for the same period in 2022. The decrease was mainly attributable to lower employee related costs due to a reduction in headcount. General and administrative expenses were $9.0 million for the six months ended June 30, 2023, as compared to $10.8 million for the same period in 2022.

Other income, net was $0.2 million for the second quarter of 2023, as compared to other expense, net of $0.9 million for the same period in 2022. Other income (expense), net primarily consisted of interest income partially offset by expense related to future royalty payments. Other income, net was $0.2 million for the six months ended June 30, 2023 compared to other expense, net $1.9 million for the same period in 2022.

Including the impact of the July Registered Direct offering, Curis’s cash, cash equivalents and investments totaled $77.4 million, and the Company had approximately 117.7 million shares of common stock outstanding. Curis expects its existing cash, cash equivalents and investments should enable it to maintain its planned operations into 2025.

Conference Call Information

Curis management will host a conference call today, August 3, 2023, at 4:30 p.m. ET, to discuss the business update and these financial results.

To access the live conference call, please dial 1-888-346-6389 from the United States or 1-412-317-5252 from other locations, shortly before 4:30 p.m. ET. The conference call can also be accessed on the Curis website in the Investors section.

On August 3, 2023 Avalo Therapeutics, Inc. (Nasdaq: AVTX), reported business updates and financial results for the second quarter of 2023 (Press release, Avalo Therapeutics, AUG 3, 2023, View Source [SID1234633741]).

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"Although the PEAK trial did not meet its primary endpoint, mechanistically I believe AVTX-002 has promise in other inflammatory driven diseases including IBD and other diseases of the lung, gut and skin. Additionally, we believe an opportunity remains in asthma, particularly in a subset of patients with higher baseline LIGHT levels. We also have high confidence in our preclinical stage fully human BTLA agonist fusion protein (AVTX-008) to potentially treat a wide range of autoimmune diseases and are excited by the drug’s novel mechanism of action and potential usage in patients not responsive to anti-TNF therapy," said Dr. Garry Neil, Chief Executive Officer and Chairman of the Board. "The team is working tirelessly to determine the best path forward for these assets, including indication selection and funding to support development."

Corporate Updates:

•In June of 2023, Avalo prepaid $6 million of principal under its loan and security agreement. As of June 30, 2023, the remaining principal payments were $15.2 million.
•On July 20, 2023, Avalo entered into a forbearance agreement with its debt lenders, pursuant to which the parties agreed that an event of default had occurred due to a material adverse change in the Company’s business and the lenders agreed to forbear from enforcing its full remedies, including acceleration of the amounts due, until August 15, 2023 or earlier triggering event.
•Avalo is considering out-licensing or sale of its non-core and potentially its core assets to increase focus and reduce future expenses. In July of 2023, Avalo entered into a non-binding letter of intent for the potential sale of AVTX-801 (D-galactose), AVTX-802 (D-mannose) and AVTX-803 (L-fucose).

Program Updates:

•AVTX-002: Anti-LIGHT monoclonal antibody (mAb) targeting immune-inflammatory diseases.
◦Avalo announced that its Phase 2 PEAK trial in patients with NEA did not meet its primary endpoint, measured by the proportion of patients who experienced an asthma-related event (ARE), however AVTX-002 demonstrated a significant and sustained reduction in LIGHT levels and a favorable safety and tolerability profile. Further, a preliminary post-hoc analyses for a sub-population of patients with baseline LIGHT levels over 125 pg/mL, which represented over 50% of patients, showed an approximately 50% reduction in AREs for patients treated with AVTX-002 compared to placebo.
◦Previously demonstrated AVTX-002 was statistically significant in reducing respiratory failure and mortality in patients hospitalized with COVID-19 ARDS in a randomized placebo-controlled trial. AVTX-002 also demonstrated positive trends in an open-label study in Crohn’s Disease.
◦AVTX-002 showed a rapid and sustained reduction of LIGHT levels in all indications studied including COVID-19 ARDS, Crohn’s Disease and NEA.
◦Avalo will continue to evaluate the topline results of the Phase 2 PEAK trial, while also pursuing funding for the program, to inform future development plans.
1

•AVTX-008: B and T Lymphocyte Attenuator (BTLA) agonist fusion protein targeting immune dysregulation disorders.
◦Avalo previously identified a lead molecule, is evaluating several immune dysregulation disorders to pursue and plans to rapidly progress the asset to IND, subject to funding.
•AVTX-803: Fucose replacement for leukocyte adhesion deficiency type II (LAD II, also known as SLC35C1-CDG), a congenital disorder of glycosylation (CDG).
◦In July of 2023, Avalo entered into a non-binding letter of intent for the potential sale of AVTX-801 (D-galactose), AVTX-802 (D-mannose) and AVTX-803 (L-fucose).

Second Quarter 2023 Financial Update:

Avalo had $6.3 million in cash and cash equivalents as of June 30, 2023, representing a $6.9 million decrease compared to December 31, 2022. The decrease was driven by operating expenditures to fund pipeline development and a $6 million partial prepayment under the loan and security agreement and were partially offset by $20.3 million of net proceeds from equity financings.

Total operating expenses decreased $17.8 million for the six months ended June 30, 2023 as compared to the same period in 2022. This decrease was primarily driven by decreases to both selling, general and administrative and research and development expenses as a result of cost savings initiatives implemented in the first quarter of 2022 and fewer programs ongoing in the current year.

The net loss and net loss per share for the three months ended June 30, 2023 was largely driven by operating expenses.

About AVTX-002 (quisovalimab)

AVTX-002 is a fully human monoclonal antibody (mAb), directed against human LIGHT (Lymphotoxin-like, exhibits Inducible expression, and competes with Herpes Virus Glycoprotein D for Herpesvirus Entry Mediator (HVEM), a receptor expressed by T lymphocytes). There is increasing evidence that the dysregulation of the LIGHT-signaling network which includes LIGHT, its receptors HVEM and LTβR and the downstream checkpoint BTLA, is a disease-driving mechanism in autoimmune and inflammatory reactions in barrier organs. Therefore, we believe reducing LIGHT levels can moderate immune dysregulation in many acute and chronic inflammatory disorders. AVTX-002 previously demonstrated proof of concept in COVID-19 induced acute respiratory distress syndrome including reduction in mortality and respiratory failure, as well as a positive signal in Crohn’s Disease.

About AVTX-008

AVTX-008 is a fully human B and T Lymphocyte Attenuator (BTLA) agonist fusion protein in the IND-enabling stage.

On August 3, 2023 BridgeBio Pharma, Inc. (Nasdaq: BBIO) (BridgeBio or the Company), a commercial-stage biopharmaceutical company focused on genetic diseases and cancers, reported its financial results for the second quarter ended June 30, 2023 and provided an update on the Company’s operations (Press release, BridgeBio, AUG 3, 2023, View Source [SID1234633740]).

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"We’ll remain ever grateful for the support of the physicians and patients in the ATTR-CM community, which helped bring the ATTRibute-CM study to its final readout," said Neil Kumar, Ph.D., founder and CEO of BridgeBio. "With these data in hand, coupled with a pipeline that could produce an additional three pivotal readouts in the next 24 months, we feel we have the ingredients to build a sustainable engine for the patients that we serve in large and small markets alike."

BridgeBio’s key programs:

Acoramidis (AG10) – Transthyretin (TTR) stabilizer for transthyretin amyloid cardiomyopathy (ATTR-CM):
In July 2023, the Company released topline results from ATTRibute-CM, its Phase 3 trial of acoramidis for patients with ATTR-CM. The primary endpoint analysis was highly statistically significant with a Win Ratio of 1.8 (p<0.0001).
A clinically meaningful and consistent treatment effect was observed across all measures of mortality, morbidity, function, and quality of life.
An on-treatment survival rate of 81% was observed, versus a placebo survival rate of 74% (absolute risk reduction of 6.43%; relative risk reduction of 25%).
A highly statistically significant relative risk reduction of 50% (p<0.0001) was observed on frequency of cardiovascular-related hospitalization.
In comparative exploratory post hoc analyses enabled by tafamidis drop-in, albeit at low patient numbers, acoramidis showed a 42% greater increase in serum TTR levels and a 92% improvement in median NT-proBNP relative to placebo + tafamidis.
Acoramidis was well-tolerated with no safety signals of potential clinical concern identified.
BridgeBio intends to file an NDA for acoramidis with the FDA by end of 2023 and marketing authorization applications with additional regulatory authorities globally in 2024.
The details of the topline results of the ATTRibute-CM trial will be presented at the annual meeting of the European Society of Cardiology, one of the premier global cardiology congresses, in Amsterdam at the end of August 2023.
Low-dose infigratinib – FGFR1-3 inhibitor for achondroplasia and hypochondroplasia:
In June 2023, the Company presented updated six-month results from Cohort 5 of PROPEL2, its Phase 2 trial of infigratinib for children with achondroplasia, at ENDO 2023; the data demonstrated a significant and robust increase in annualized height velocity (AHV) with a mean change from baseline of +3.38 cm/year for 12 children.
83% of children in Cohort 5 responded to infigratinib, as defined by an increase from baseline AHV of at least 25%. The mean change from baseline in AHV of responders was +4.08 cm/year.
Early but promising trends towards improvement in proportionality were observed, as measured by the upper and lower body segment ratio.
At six months, infigratinib was well-tolerated as a single daily oral therapy with no adverse events assessed as treatment-related in all patients in Cohort 5.
The Company has started to enroll children in the run-in for a registrational Phase 3 trial.
If approved, BridgeBio believes that infigratinib has the potential to capture a significant share of the market based on blinded market research.
BBP-418 – Glycosylation substrate for limb-girdle muscular dystrophy type 2I/R9 (LGMD2I/R9):
The Company met with the FDA to discuss the use of glycosylated αDG levels as a surrogate endpoint. Based on this meeting, the Company believes there is potential to pursue Accelerated Approval in the U.S. for BBP-418.
The Company has dosed the first participant in FORTIFY, its global Phase 3 study of BBP-418 in patients with LGMD2I/R9.
FORTIFY includes an interim analysis at 12 months focused on change in glycosylated αDG levels; topline data from this analysis is expected in late 2024/early 2025.
Deficiency of glycosylated αDG is the causal molecular driver of LGMD2I/R9. In the ongoing Phase 2 study, patients treated with BBP-418 had a rapid and sustained increase of glycosylated αDG levels, concurrent with sustained decreases in creatine kinase and improvements from baseline in ambulatory and clinical function measures.
BBP-418 has a potentially addressable population of 7,000 patients in the United States and European Union.
There are currently no disease-modifying treatments available for LGMD2I/R9.
Encaleret – Calcium-sensing receptor (CaSR) inhibitor for autosomal dominant hypocalcemia type 1 (ADH1):
The Company presented 18-month data from the long-term extension of its Phase 2 study of encaleret in patients with ADH1 at ENDO 2023, including observations of a rapid and sustained treatment effect. Additionally, the Company shared initial findings from its genetic testing program, highlighting that ADH1 may be the most common presentation of nonsurgical hypoparathyroidism.
Population genetics analyses estimate approximately 25,000 carriers of gain-of-function variants of the CaSR, the underlying cause of ADH1, in the United States and European Union.
The Company anticipates sharing topline data from CALIBRATE, a Phase 3 registrational trial of encaleret for ADH1, in the first half of 2024.
If approved, encaleret could be the first therapy specifically indicated for the treatment of ADH1.
BBP-631 – AAV5 gene therapy candidate for congenital adrenal hyperplasia (CAH):
The Phase 1/2 gene therapy trial of BBP-631 for CAH continued to progress, and the Company plans to provide an update by the end of 2023.
CAH is one of the most prevalent genetic diseases potentially addressable with adeno-associated virus (AAV) gene therapy, with more than 75,000 cases estimated in the United States and European Union.
RAS cancer portfolio:
BridgeBio is continuing to develop the three main programs of its RAS franchise:
BBO-8520, an investigational, next-generation small molecule direct KRASG12C(ON) inhibitor candidate that is designed to directly bind and inhibit KRASG12C in both its ON (GTP-bound) and OFF (GDP-bound) conformations, which remains on track to file an IND application and enter the clinic in 2023.
A PI3Kα:RAS breaker program, investigational small molecules that are designed to block RAS-driven PI3Kα activation with a novel and potentially broad mechanism of action to target not only PI3Kα mutant tumors and RAS mutant tumors, but potentially other tumors driven by RTK activation of RAS signaling. The Company has selected a development candidate and expects to file an IND application in 2024 as the second investigational RAS cancer therapy from the BridgeBio portfolio.
The Company’s pan-KRAS program, which targets multiple KRAS mutants including KRASG12D and KRASG12V, which are present in a large percentage of colorectal, pancreatic, and non-small cell lung cancer tumors. Development candidate selection for this program is planned for late 2023 or early 2024.
Recent Corporate Updates:

Partnership with Burjeel Holdings on project ‘NADER’ (Needs Assessment and Therapeutics Development for Rare Diseases – ‘nader’ meaning ‘rare’ in Arabic): Signed a preliminary, non-binding Collaboration Agreement establishing a mutual intention to revolutionize the field of early diagnosis and treatment of rare diseases in the United Arab Emirates and the region.
Updated encouraging clinical and biomarker data shared for the Company’s Canavan disease gene therapy program: Presented promising positive data from six participants dosed in CANaspire, the Company’s Phase 1/2 clinical trial of BBP-812, an investigational intravenous (IV) adeno-associated virus serotype 9 (AAV9) gene therapy for the treatment of Canavan disease. Following treatment, the N-acetylaspartate (NAA) levels of CANaspire participants were consistent with levels seen in individuals with milder Canavan disease based on findings from the Company’s natural history study and reports in the scientific literature. Sustained reductions in NAA were measured in the urine, cerebrospinal fluid (CSF), and brain of all participants and have been observed for over one year in the earliest dosed participants.
Second Quarter 2023 Financial Results:

Cash, Cash Equivalents, Marketable Securities and Short-Term Restricted Cash

Cash, cash equivalents, marketable securities and short-term restricted cash, totaled $353.2 million as of June 30, 2023, compared to $466.2 million as of December 31, 2022. The net decrease of $113.0 million in cash, cash equivalents, marketable securities and short-term restricted cash is primarily attributable to net cash used in operating activities of $257.7 million, offset by net proceeds received of $144.0 million from the Follow-on public offering during the six months ended June 30, 2023.

Revenue

Revenue for the three and six months ended June 30, 2023 was $1.6 million and $3.5 million, respectively, as compared to $73.7 million and $75.4 million for the same periods in the prior year. Revenue for the three and six months ended June 30, 2023 primarily consisted of $1.5 million and $3.2 million, respectively, of services revenue under the Navire-BMS License Agreement. Revenue for the three and six months ended June 30, 2022 primarily consisted of $70.2 million of license revenue and $3.2 million of services revenue under the Navire-BMS License Agreement.

Operating Costs and Expenses

Operating costs and expenses for the three and six months ended June 30, 2023 were $147.7 million and $275.7 million, respectively, compared to $153.9 million and $329.3 million for the same periods in the prior year. The overall decrease in operating costs and expenses for the three and six months ended June 30, 2023 compared to the comparative periods was due mainly to the decreases in research, development and other (R&D) expenses resulting from the Company’s reprioritization of its R&D programs; selling, general and administrative expenses resulting from its company-wide streamlining of costs; and restructuring, impairment and related charges since the majority of the restructuring initiatives commenced in the first quarter of 2022. The effects of the Company’s restructuring initiative which commenced in the first quarter of 2022, continue to be realized due to the Company’s reductions in operating costs and expenses. Restructuring, impairment and related charges for the three and six months ended June 30, 2023, amounted to $3.5 million and $6.9 million, respectively. These charges primarily consisted of winding down, exit costs, and severance and employee-related costs. Restructuring, impairment and related charges for the same periods in the prior year were $8.4 million and $31.1 million, respectively. These charges primarily consisted of impairments and write-offs of long-lived assets, severance and employee-related costs, and exit and other related costs. The Company remains committed to evaluating various restructuring alternatives aimed at driving operational changes in business processes. These alternatives includes enhancing commercialization efforts, improving efficiencies, and achieving cost savings.

Stock-based compensation expenses included in operating costs and expenses for the three months ended June 30, 2023 were $27.2 million, of which $13.2 million is included in research, development and other (R&D) expenses, $14.0 million is included in selling, general and administrative expenses. Stock-based compensation expenses included in operating costs and expenses for the three months ended June 30, 2022 were $28.3 million, of which $14.3 million is included in research, development and other (R&D) expenses, and $14.0 million is included in selling, general and administrative expenses.

Stock-based compensation expenses included in operating costs and expenses for the six months ended June 30, 2023 were $50.7 million, of which $25.0 million is included in research, development and other (R&D) expenses, $25.7 million is included in selling, general and administrative expenses. Stock-based compensation expenses included in operating costs and expenses for the six months ended June 30, 2022 were $52.6 million, of which $22.9 million is included in research, development and other (R&D) expenses, $28.5 million is included in selling, general and administrative expenses, and $1.2 million is included in restructuring, impairment and related charges.

"Following the recent announcement and strength of our Phase 3 ATTRibute-CM data, we will continue to explore multiple options to fully resource the acoramidis launch while optimizing cost of capital, including partnerships, royalty transactions, and equity financing," said Brian Stephenson, Ph.D., CFA, Chief Financial Officer of BridgeBio. "We anticipate $300-$350 million of investment will support acoramidis from here through the first 12 months of commercial launch. This coupled with our slate of pivotal readouts over the next 24 months offers the opportunity for meaningful value creation for both patients and investors."

On August 3, 2023 BioCryst Pharmaceuticals, Inc. (Nasdaq:BCRX) reported financial results for the second quarter ended June 30, 2023, and provided a corporate update (Press release, BioCryst Pharmaceuticals, AUG 3, 2023, View Source [SID1234633739]).

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"Our strong second quarter keeps us firmly on track to achieve no less than $320 million in ORLADEYO revenue this year, as our base of patients grows larger and larger every quarter. While ORLADEYO revenues continue to grow, we are also excited to host an R&D day in November to introduce new molecules and programs from our discovery platform that have the potential to replicate or exceed the success of ORLADEYO," said Jon Stonehouse, president and chief executive officer of BioCryst.

Program Updates

ORLADEYO (berotralstat): Oral, Once-daily Treatment for Prevention of Hereditary Angioedema (HAE) Attacks

"The significant step-up in revenue we expected and achieved in the second quarter reflects the continued strong growth in patients taking ORLADEYO, the normal seasonality in revenue that follows first quarter prescription reauthorizations, and our steady improvement in helping patients get to reimbursed therapy. We recently attended the HAEA summit, attended by 1,200 patients and family members. Their strong interest and enthusiasm gave us even more confidence in our expectations for sustained long-term demand for ORLADEYO in the U.S. and globally," said Charlie Gayer, chief commercial officer of BioCryst.

ORLADEYO net revenue in the second quarter of 2023 was $81.0 million (+24.2 percent year-over-year (y-o-y)).

Total growth in patients taking ORLADEYO continued on a strong, linear trajectory.

The percentage of U.S. ORLADEYO patients receiving paid drug improved in the second quarter as the company made progress converting commercially-insured patients who had been receiving long-term free product, and as patients who received temporary free product during the first quarter prescription re-authorization process returned to reimbursed product in the second quarter.

Sales from outside the U.S. contributed 10.1 percent of global ORLADEYO net revenues in the second quarter.

The ongoing APeX-P trial in pediatric HAE patients who are 2 to <12 years of age continues to enroll as expected.
BCX10013—Oral Factor D Inhibitor

"Our goal with BCX10013 is to bring a best-in-class molecule to physicians and patients. That means a safe, highly effective, once-daily oral therapy, and we are now focused on preparing for enrollment in our dose-ranging trial in patients," said Dr. Helen Thackray, chief research and development officer.

The company has begun opening clinical trial sites for a dose-ranging trial in patients with paroxysmal nocturnal hemoglobinuria (PNH) and expects to begin patient enrollment (in countries without other approved therapies) by the end of the year. The trial is designed to identify a safe, effective, once-daily dose that BioCryst can advance into a pivotal program in renal complement-mediated diseases.

The company also plans to complete an additional cohort of its multiple ascending dose trial (MAD) of BCX10013, at a higher dose (160 mg QD), in healthy volunteers to provide further information to the pharmacokinetic model.
Upcoming R&D Day—November 3, 2023

BioCryst will host a Research and Development (R&D) day at 1:00p ET on Friday, November 3 at its Research Center of Excellence in Birmingham, AL (the event also will be webcast live). At the R&D day, the company plans to introduce additional assets from its pipeline targeting rare diseases.

Second Quarter 2023 Financial Results

For the three months ended June 30, 2023, total revenues were $82.5 million, compared to $65.5 million in the second quarter of 2022 (+25.9 percent year-over-year (y-o-y)). The increase was primarily due to $81.0 million in ORLADEYO net revenue in the second quarter of 2023, compared to $65.2 million in ORLADEYO net revenue in the second quarter of 2022 (+24.2 percent y-o-y).

R&D expenses for the second quarter of 2023 decreased to $51.2 million from $62.0 million in the second quarter of 2022 (-17.3 percent y-o-y), primarily due to decreased investment in both the BCX9250 and complement programs, partially offset by increased investment in the early-stage pipeline.

Selling, general and administrative expenses for the second quarter of 2023 increased to $51.0 million, compared to $38.0 million in the second quarter of 2022 (+34.1 percent y-o-y). The increase was primarily due to increased investment to support the commercial launch of ORLADEYO and expanded international operations.

Interest expense was $28.9 million in the second quarter of 2023, compared to $24.0 million in the second quarter of 2022 (+20.4 percent y-o-y). The increase is primarily driven by additional interest to service the Pharmakon debt secured in April 2023.

Net loss for the second quarter of 2023 was $75.3 million, or $0.40 per share, compared to a net loss of $58.9 million, or $0.32 per share, for the second quarter of 2022. There was a $29.0 million one-time debt extinguishment fee related to the close-out of the Athyrium debt facility. Excluding this one-time event, non-GAAP net loss for the second quarter of 2023 was $0.24 per share.

Cash, cash equivalents, restricted cash and investments totaled $415.7 million at June 30, 2023, compared to $418.9 million at June 30, 2022. Operating cash use for the second quarter of 2023 was $13.5 million.

Non-GAAP Pro forma Financial Measures

The information furnished in this release includes non-GAAP pro forma financial measures that differ from measures calculated in accordance with generally accepted accounting principles in the United States of America (GAAP), including financial measures labeled as "non-GAAP" or "adjusted."

We believe providing these non-GAAP measures, which show our pro forma results with these items adjusted, is valuable and useful since they allow the company and investors to better understand the company’s financial performance in the absence of these one-time events and allow investors to more accurately understand our second quarter 2023 results and more easily compare them to future results. These non-GAAP pro forma measures also correspond with the way we expected Wall Street analysts to compare our results. Our non-GAAP pro forma measures should be considered only as supplements to, and not as substitutes for or in isolation from, our other measures of financial information prepared in accordance with GAAP, such as GAAP revenue, operating income, net income, and earnings per share.

Our references to our second quarter 2023 and first six months 2023 "non-GAAP pro forma" financial measures of adjusted net loss and adjusted earnings per share constitute non-GAAP financial measures. They refer to our GAAP results, adjusted to show the results without the one-time loss on the extinguishment of the Athyrium term loans.

Financial Outlook for 2023

The company expects full year 2023 global net ORLADEYO revenue to be no less than $320 million. Operating expenses for full year 2023, not including non-cash stock compensation, are expected to be flat to 2022 at approximately $375 million. While flat year-over-year, we expect reductions in R&D spending in 2023 following the discontinuation of the BCX9930 and BCX9250 programs in 2022 and the delay in the BCX10013 clinical program, offset by increases in SG&A to support the U.S. launch and global expansion of ORLADEYO.

Conference Call and Webcast

BioCryst management will host a conference call and webcast at 8:30 a.m. ET today to discuss the financial results and provide a corporate update. The live call may be accessed by dialing 1-866-777-2509 for domestic callers and 1-412-317-5413 for international callers. A live webcast and replay of the call will be available online in the investors section of the company website at www.biocryst.com.

On August 3, 2023 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, 2023 and provided recent corporate updates (Press release, Bicycle Therapeutics, AUG 3, 2023, View Source [SID1234633738]).

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"We have made significant progress in the first half of 2023 executing on our plan to become one of the world’s leading solid tumor medicines companies," said Kevin Lee, Ph.D., Chief Executive Officer of Bicycle Therapeutics. "Not only have we continued to advance our three clinical trial candidates – BT5528, BT8009 and BT7480 – but we have also entered into multiple research and development collaborations with pioneers in the radiopharmaceutical space to develop Bicycle radio-conjugates (BRCs). These collaborations enable us to advance a broad pipeline of partnered and wholly owned BRCs that represents the third pillar of our oncology strategy beyond our Bicycle toxin conjugate (BTC) and Bicycle tumor-targeted immune cell agonist (Bicycle TICA) programs. Our clinical programs remain on track for us to provide updates in the second half of 2023. Additionally, we are excited to welcome Alethia Young, our new Chief Financial Officer, who brings over 20 years of experience in the healthcare and biotech industry to Bicycle. The advancement of our programs and platform in oncology and beyond are supported by a strong balance sheet that has been further enhanced by the recent proceeds from a public equity offering completed in July."

Second Quarter 2023 and Recent Highlights

Raised Gross Proceeds of $230.0 Million in Public Offering. In July 2023, Bicycle announced the closing of an underwritten public offering resulting in gross proceeds of approximately $230.0 million, including the full exercise of the underwriters’ option to purchase additional shares. Net proceeds were approximately $215.5 million. In addition, the company also received gross proceeds from Bicycle’s at-the-market (ATM) offering program during the second quarter of 2023 totaling $12.5 million.

Continued Progress with Clinical and Regulatory Programs Including BT8009, BT5528, and BT7480. Enrollment in the company’s clinical trial of BT8009, as well as discussions with the U.S. Food and Drug Administration (FDA) remain ongoing. The company expects to provide clinical and regulatory updates on BT8009 in the second half of 2023.
Enhanced Leadership Team with Appointment of Alethia Young as Chief Financial Officer. In June 2023, Bicycle announced the appointment of Alethia Young as its new Chief Financial Officer, effective July 17. Ms. Young brings to Bicycle more than 20 years of experience in the healthcare and biotech industry, most recently serving as the Chief Financial Officer at Graphite Bio. Prior to Graphite Bio, she served as a senior biotech analyst and head of research at Cantor Fitzgerald, and previously held senior biotech analyst positions at Credit Suisse and Deutsche Bank.
Presented Potent Anti-Tumor Activity of a Lead-212 Labelled MT1-MMP Targeting Bicycle Radionuclide Conjugate at TIDES 2023. In May 2023, Bicycle presented preclinical results from a preclinical research collaboration with OranoMed. In these studies, Pb-BCY20603, a prototype BRC that binds with high affinity to the tumor antigen MT1-MMP and carries a chelate of lead-212, showed potent anti-tumor activity in rodent tumor xenograft studies and achieved complete tumor regressions after 3 dosing cycles of 10 µCi, given two weeks apart. Median survival was increased for each dosing group with 90% survival observed for the 3 cycles of 10 μCi, treatment at the end of the 100-day study.

Announced Multiple Strategic Collaborations for Developing BRCs for Potential Oncology Targets
Strategic Collaboration with Bayer. In May 2023, Bicycle announced that it has entered into a strategic collaboration agreement with Bayer to discover, develop, manufacture, and commercialize BRCs for multiple agreed upon oncology targets. Bicycle will use its proprietary phage platform to develop bicyclic peptides, while Bayer will be responsible for, and fully fund, all further preclinical and clinical development, manufacturing, and commercialization activities. Bicycle received a $45 million upfront payment in July 2023 and, with potential development and commercial-based milestone fees, payments under the collaboration to Bicycle could total up to $1.7 billion. Bicycle will also be eligible to receive tiered royalties on Bicycle-based medicines commercialized by Bayer.
Expanded Collaboration with the German Cancer Research Center. In May 2023, Bicycle announced the extension of a collaboration with the German Cancer Research Center (DKFZ) to develop and discover BRCs for potential oncology targets. This enhanced relationship will provide a more continuous and purpose-driven commitment towards advancing Bicycle’s wholly owned BRC candidates. Bicycle intends to commence initial testing of its wholly owned BRCs in patients during 2024.

Strategic Collaboration with Novartis. In March 2023, Bicycle announced a strategic collaboration with Novartis to collaborate on the discovery, development and commercialization of BRCs for multiple agreed upon oncology targets. Bicycle will utilize its proprietary phage platform to discover Bicycles to be developed into BRCs. Novartis will be responsible for and fund further development, manufacture and commercialization of the BRCs. Under the collaboration, Bicycle received a $50 million upfront payment in April 2023 and is eligible for development and commercial-based milestone payments totaling up to $1.7 billion. Bicycle will also be eligible to receive tiered royalties on Bicycle-based medicines commercialized by Novartis.
Financial Results

Cash and cash equivalents were $340.4 million as of June 30, 2023, compared to $339.2 million as of December 31, 2022. The increase in cash and cash equivalents is primarily due to $50.0 million received from our collaboration agreement with Novartis and $14.8 million of net proceeds from our ATM offering program, offset by cash used in operating activities. Our cash and cash equivalents at June 30, 2023 do not include the upfront payment from Bayer or proceeds from our public offering received in July 2023. Additionally in July, the company strengthened its balance sheet with gross proceeds of $230.0 million, or net proceeds of approximately $215.5 million, from the July 2023 public offering.

Research and development expenses were $39.7 million for the three months ended June 30, 2023, compared to $19.9 million for the three months ended June 30, 2022. The increase in expense of $19.9 million was primarily due to increased clinical program expenses for BT8009, BT7480 development expenses, and other discovery and platform related expenses, as well as increased personnel-related expenses, including incremental non-cash share-based compensation expense of $1.3 million, offset by incremental UK research and development incentives.
General and administrative expenses were $14.8 million for the three months ended June 30, 2023, compared to $11.8 million for the three months ended June 30, 2022. The increase of $3.0 million for the three months ended June 30, 2023 as compared to the same period in the prior year was primarily due to an increase in professional and consulting fees, as well as an increase in personnel-related expenses, including incremental non-cash share-based compensation expense of $1.2 million, offset by a favorable impact of foreign exchange rates.
Net loss was $42.6 million, or $(1.41) basic and diluted net loss per share, for the three months ended June 30, 2023, compared to net loss of $26.8 million, or $(0.90) basic and diluted net loss per share, for three months ended June 30, 2022.