On August 5, 2022 Nuvalent, Inc. (Nasdaq: NUVL), a clinical-stage biopharmaceutical company focused on creating precisely targeted therapies for clinically proven kinase targets in cancer, reported new preclinical data supporting the potential best-in-class profile of NVL-655 – an ALK-selective inhibitor, and a "Trial in Progress" poster for the Phase 1/2 ARROS-1 study of NVL-520 – a ROS1-selective inhibitor (Press release, Nuvalent, AUG 5, 2022, View Source [SID1234617668]). NVL-520 and NVL-655 are central nervous system (CNS)-penetrant kinase inhibitors designed to specifically solve for the dual challenges of kinase resistance and selectivity commonly observed with currently available inhibitors.

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The two posters will be presented at the IASLC 2022 World Conference on Lung Cancer (WCLC) Annual Meeting taking place August 6-9, 2022 in Vienna, Austria. The posters will also be available on the Nuvalent website.

"Our presentations at WCLC showcase the value that our collaborations with leading physician-scientists and translational investigators bring towards characterizing and developing our parallel lead programs for patients with non-small cell lung cancer (NSCLC)," said James Porter, Ph.D., Chief Executive Officer of Nuvalent. "We are grateful for our continued collaborations focused on advancing the understanding of resistance to kinase inhibitors, as well as the dedication and support of the Phase 1 clinical investigators participating in our ongoing studies for patients with advanced NSCLC and other solid tumors."

"We selected NVL-520 and NVL-655 based on the demonstrated strength of their preclinical profiles and their potential to drive deep, durable responses for patients with ROS1-positive and ALK-positive cancers, respectively. With both programs now under clinical investigation, we remain committed to continued, rigorous preclinical characterization to both deepen our understanding of our programs as well as to support the advancement of tools and models that may help accelerate the development of new therapies for genomically-driven cancers," said Henry Pelish, Ph.D., Vice President of Biology at Nuvalent. "We are pleased to share data further characterizing NVL-655 in a new patient-derived model of lorlatinib-resistant ALK-positive NSCLC with the treatment-emergent G1202R/T1151M compound resistance mutation, developed by our clinical and translational collaborators at Gustave Roussy."

The MR448re patient-derived model was established from cancer cells retrieved from a NSCLC patient previously treated with four prior ALK kinase inhibitors and most recently progressing following treatment with lorlatinib. Presence of an EML4-ALK fusion and the G1202R/T1151M compound mutation was confirmed by sequencing.

"The rapid development of the MR448re patient-derived model and subsequent evaluation of NVL-655 is a testament to the efficient cooperation between our clinical and translational investigators, and our collaborators at Nuvalent," said Luc Friboulet, Ph.D., investigator at Gustave Roussy. "NVL-655 showed strong antitumor activity in this heavily refractory model, while lorlatinib showed limited inhibitory activity consistent with treatment history. This further supports the differentiating and potentially best-in-class preclinical profile of NVL-655, which has previously demonstrated the ability to retain activity in the presence of a broad spectrum of single and compound ALK resistance mutations while maintaining a wide selectivity window over TRKB."

A "Trial in Progress" poster summarizing the preclinical profile of NVL-520 and clinical trial design of the Phase 1/2 ARROS-1 study (NCT05118789) for NVL-520 will also be presented. This multicenter, open-label, dose-escalation and expansion trial is designed to evaluate NVL-520 as an oral monotherapy for patients with advanced ROS1-positive NSCLC and other solid tumors. The ongoing Phase 1 dose-escalation portion of the study is currently enrolling ROS1-positive NSCLC patients who have previously received at least one ROS1 TKI, or patients with other ROS1-positive solid tumors previously treated with any prior therapy. Nuvalent plans to share preliminary dose-escalation data from ARROS-1 in the second half of 2022.

WCLC Presentation Overview:

Title: Preclinical Activity of NVL-655 in a Patient-Derived NSCLC Model with Lorlatinib-Resistant ALK G1202R/T1151M Mutation
Authors: H. Mizuta1, L. Bigot1, A. Tangpeerachaikul2, H.E. Pelish2, L. Friboulet1
Abstract Number: EP08.02-020
Session Category: Metastatic Non-small Cell Lung Cancer
Session Title: Molecular Targeted Treatments
Session Date and Time: August 7, 2022, 9:45am – 6:00pm CEST

1Gustave-Roussy, Villejuif, France; 2Nuvalent, Inc., Cambridge, MA, USA

Summary of Presentation:

ALK G1202R single and compound mutations are recurrent mechanisms of resistance to previous-generation therapies, including alectinib and lorlatinib.
NVL-655 showed strong antitumor activity in preclinical models derived from ALK positive patients who have progressed on treatment with earlier-generation ALK inhibitors, including a G1202R/T1151M compound mutation model derived from a patient previously treated with crizotinib, alectinib, brigatinib, and lorlatinib.
Among all inhibitors tested, NVL-655 continues to show the broadest activity across ALK fusion partners and resistance mutations while maintaining a wide selectivity window over TRKB.
NVL-655 is currently being evaluated in the Phase 1/2 ALKOVE-1 study for patients with advanced ALK+ NSCLC and other solid tumors, including those with ALK resistance mutations and CNS metastases (NCT05384626).
Title: NVL-520, a Highly Selective ROS1 Inhibitor, in Patients with Advanced ROS1-Positive Solid Tumors: The Phase 1/2 ARROS-1 Study
Authors: A. Drilon1, S-H.I. Ou2, S. Gadgeel3, M. Johnson4, A. Spira5, G. Lopes6, B. Besse7, E. Felip8, A.J. van der Wekken9, A. Calles10, M.J. de Miguel11, D.R. Camidge12, Y. Elamin13, S. Liu14, J. Bauman15, D. Haggstrom16, G. Riley17, H.E. Pelish17, V.W. Zhu17, J.J. Lin18
Abstract Number: EP08.02-041
Session Category: Metastatic Non-small Cell Lung Cancer
Session Title: Molecular Targeted Treatments
Session Date and Time: August 7, 2022, 9:45am – 6:00pm CEST

1Memorial Sloan Kettering Cancer Center, New York/NY/USA ,2University Of California Irvine Medical Center, Orange/CA/USA ,3Henry Ford Cancer Institute, Detroit/MI/USA ,4Sarah Cannon Research Institute, Nashville/TN/USA,5NEXT Oncology – Virginia Cancer Specialists, Fairfax/VA/USA ,6Sylvester Comprehensive Cancer Center at the University of Miami and the Miller School of Medicine, Miami/FL/USA ,7Institut Gustave Roussy, Villejuif Cedex/FR,8Hospital Vall d’Hebron, Barcelona/ES ,9University of Groningen, University Medical Centre Groningen,Groningen/NL ,10Hospital Universitario Gregorio Marañón, Madrid/ES ,11START Madrid-HM CIOCC, Madrid/ES,12University of Colorado Cancer Center, Anschutz Medical Campus, Aurora/CO/USA ,13MD Anderson Cancer Center, Houston/TX/USA ,14Georgetown University, Washington/DC/USA ,15Fox Chase Cancer Center, Philadelphia/PA/USA,16Levine Cancer Institute, Atrium Health, Charlotte/NC/USA ,17Nuvalent, Inc., Cambridge/MA/USA ,18Massachusetts General Hospital, Boston/MA/USA

Summary of Presentation:

NVL-520 has demonstrated CNS activity and potent and selective inhibition of ROS1 & ROS1 G2032R over TRKB in preclinical models. These data indicate the potential to minimize TRK-related CNS adverse events seen with dual TRK/ROS1 inhibitors and drive more durable responses for patients with ROS1+ tumors, including those with ROS1 resistance mutations and CNS metastases.
ARROS-1 is a Phase 1/2 study evaluating the safety and activity of NVL-520 in patients with advanced ROS1+ NSCLC and other solid tumors, including those with ROS1 resistance mutations and CNS metastases.
The Phase 1 portion of the study is open and actively enrolling in the USA, Spain, the Netherlands, and France, with further global expansion planned.
Phase 2 cohorts are designed to support potential registration in TKI-naive or previously treated ROS1+ NSCLC.
About NVL-655

NVL-655 is a novel brain-penetrant ALK-selective inhibitor created to overcome limitations observed with currently available ALK inhibitors. NVL-655 is designed to remain active in tumors that have developed resistance to first-, second-, and third-generation ALK inhibitors, including tumors with the solvent front G1202R mutation or compound mutations G1202R / L1196M ("GRLM"), G1202R / G1269A ("GRGA"), or G1202R/L1198F ("GRLF"). NVL-655 has been optimized for CNS penetrance to improve treatment options for patients with brain metastases. NVL-655 has been observed in preclinical studies to selectively inhibit wild-type ALK and its resistance variants over the structurally related tropomyosin receptor kinase (TRK) family to potentially avoid TRK-related CNS adverse events seen with dual TRK/ALK inhibitors and drive more durable responses for patients. NVL-655 is currently being investigated in the ALKOVE-1 study (NCT05384626), a first-in-human Phase 1/2 clinical trial for patients with advanced ALK-positive non-small cell lung cancer (NSCLC) and other solid tumors.

About NVL-520

NVL-520 is a novel brain-penetrant ROS1-selective inhibitor designed to remain active in tumors that have developed resistance to currently available ROS1 inhibitors, including tumors with the prevalent G2032R resistance mutation and those with the S1986Y/F, L2026M, or D2033N resistance mutations. NVL-520 has been optimized for brain penetrance to potentially improve treatment options for patients with brain metastases. NVL-520 has been observed in preclinical studies to selectively inhibit wild-type ROS1 and its resistance variants over the structurally related tropomyosin receptor kinase (TRK) family to potentially avoid TRK-related CNS adverse events seen with dual TRK/ROS1 inhibitors and drive more durable responses for patients. NVL-520 is currently being investigated in the ARROS-1 study (NCT05118789), a first-in-human Phase 1/2 clinical trial for patients with advanced non-small cell lung cancer (NSCLC) and other solid tumors.

On August 5, 2022 Kazia Therapeutics Limited (NASDAQ: KZIA; ASX: KZA), an oncology-focused drug development company, reported the presentation of promising new data from an ongoing phase I clinical trial of paxalisib in combination with radiotherapy for the treatment of brain metastases, sponsored by Memorial Sloan Kettering Cancer Center in New York, NY (Press release, Kazia Therapeutics, AUG 5, 2022, View Source [SID1234617697]).

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Interim data from the first stage of the study reports that all 9 evaluable patients experienced complete or partial response, representing an overall response rate (ORR) of 100%. For comparison, a typical ORR associated with whole brain radiotherapy alone can commonly range from 20-45% in published studies, of which some representative examples are indicated below.

The data has been accepted for an oral presentation at the upcoming 2022 Annual Conference on CNS Clinical Trials and Brain Metastases, jointly organised by the Society for Neuro-Oncology (SNO) and the American Society for Clinical Oncology (ASCO) (Free ASCO Whitepaper), and held in Toronto, Canada from 12-13 August 2022.

Key Points

Approximately 200,000 cancer patients develop brain metastases in the United States each year. Brain metastases are typically very challenging to treat and are associated with poor prognosis. Radiotherapy remains a mainstay of clinical management.

Dr. Jonathan Yang, Director, Metastatic Disease, Department of Radiation Oncology at Memorial Sloan Kettering Cancer Center is the Principal Investigator of this clinical trial that is examining the combination of paxalisib with whole brain radiotherapy for patients with brain metastases (NCT04192981). The trial is designed in two stages: an initial exploratory stage and a confirmatory expansion stage.

9 of 12 patients in the initial stage were evaluable for efficacy. All 9 patients exhibited complete or partial response, according to RANO-BM criteria, representing an ORR of 100%.

The patients comprised a range of primary tumours, with breast cancer the most common, representing one third of patients.

The safety profile of paxalisib in combination was broadly consistent with monotherapy experience in other clinical trials, and a maximum tolerated dose (MTD) of 45mg daily in combination with radiotherapy was confirmed.

Recruitment to the expansion stage has already commenced, with the objective of recruiting an additional 12 patients.
Kazia CEO, Dr. James Garner, commented, "We are encouraged by this data and by the potential benefit it may indicate to this substantial and high-need group of patients. Radiotherapy is a ubiquitous component of the treatment paradigm for brain metastases, but resistance is common. Dr. Yang’s study has shown a very promising signal that paxalisib may help to potentiate the effect of radiotherapy. We also learned recently that the ongoing Alliance study in brain metastases had graduated to an expansion stage in the breast cancer cohort, so this now represents the second positive signal for paxalisib in brain metastases, which we increasingly believe represents a very promising opportunity for the product candidate."

Brain Metastases

It is estimated that as many as 20% of all patients with cancer will develop brain metastases (secondary tumours in the central nervous system). The most common primary tumours that spread to the brain include lung, breast, colorectal, melanoma, and renal cell carcinoma. Median overall survival for patients diagnosed with brain metastases ranges from 2.3 to 7.7 months.[1] It is estimated that approximately 200,000 patients are diagnosed with brain metastases each year in the United States alone.[2]

Radiotherapy is the mainstay of treatment for brain metastases, and generally consists in either stereotactic radiosurgery (SRS) or whole brain radiotherapy (WBRT) or some combination thereof. The efficacy of WBRT differs according to the type of tumour and the number and volume of brain metastases, but several recent publications cite overall response rates of 20-45%.

Clinical Study Rationale and Design

Research by Dr. Yang and others has shown that activation of the PI3K pathway is common in brain metastases, even in some cases where it is not present in the primary tumour. Moreover, PI3K pathway activation appears to be induced by radiotherapy, and to confer upon the tumour resistance to radiotherapy. These observations provide a strong rationale for testing the combination of a brain-penetrant PI3K inhibitor with radiotherapy.

This phase I study is a single-arm prospective trial comprising patients with brain metastases or leptomeningeal metastases from any primary tumour. The primary objective is safety and tolerability. All patients have PI3K pathway mutations at baseline. The first stage of the study is intended to establish the MTD of paxalisib in combination with WBRT and to characterise safety and tolerability. The second stage is intended to elicit confirmatory signals of efficacy, with the intent to recruit a further 12 patients.

Next Steps

Enrolment to the second stage of the study is already underway and we currently estimate preliminary data from the second part of the phase I clinical trial in CY2023.

Kazia expects to discuss emerging data from this study, along with other research in brain metastases, with its scientific advisors and regulatory consultants in due course, with potential FDA consultation at a future date.

Summary of Abstract

Session 2: Multimodality Approaches to Primary and Secondary Brain Tumors – Invited
Speakers and Oral Abstracts
Friday, 12 August 2022
11am – 1pm

Abstract MMAP-05 – Phase I study of concurrent paxalisib and radiation therapy in patients with solid tumor brain metastases or leptomeningeal metastases harboring PI3K pathway mutations: results from the dose-escalation cohort (NCT04192981)
Lead Author: T Jonathan Yang, MD, PhD
Institution: Memorial Sloan Kettering Cancer Center, New York, NY

On August 4, 2022 IMV Inc. (Nasdaq: IMV; TSX: IMV) ("IMV" or "the Company"), a clinical-stage company developing a portfolio of immune-educating therapies based on its novel DPX platform to treat solid and hematologic cancers, reported that it will hold a conference call and webcast on Thursday, August 11, 2022, at 8:00 a.m. ET to discuss the company’s 2022 second quarter financial and operational results (Press release, IMV, AUG 4, 2022, View Source [SID1234617470]).

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Financial analysts are invited to join the conference call by registering at this link prior the call to receive their individual dial-in information.

Other interested parties will be able to access the live audio webcast by registering on IMV website: View Source The webcast will be recorded and will then be available on the IMV website for 30 days following the call.

On August 4, 2022 Panbela Therapeutics, Inc. (Nasdaq: PBLA), a clinical stage company developing disruptive therapeutics for the treatment of patients with urgent unmet medical needs, reported it has received approval from the Australian Human Research Ethics Committee (HREC) to expand the company’s global clinical trial to Australia, to study SBP-101 in combination with Gemcitabine and Nab-Paclitaxel in patients with metastatic pancreatic ductal adenocarcinoma, which is referred to as the ASPIRE trial (Press release, Panbela Therapeutics, AUG 4, 2022, View Source [SID1234617518]). The ASPIRE trial is designed as a randomized double-blind placebo-controlled trial, with a primary endpoint of overall survival.

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Australia marks the second country activated, with approximately 90 additional sites expected to be activated across 10 countries by early 2023. Panbela has commenced screening for eligible patients, with enrollment to the interim analysis expected to complete in early 2024.

About our Pipeline

The pipeline consists of assets currently in clinical trials with an initial focus on familial adenomatous polyposis (FAP), first-line metastatic pancreatic cancer, neoadjuvant pancreatic cancer, colorectal cancer prevention and ovarian cancer. The combined development programs have a steady cadence of catalysts with programs ranging from pre-clinical to registration studies.

SBP-101

SBP-101 is a proprietary polyamine analogue designed to induce polyamine metabolic inhibition (PMI) by exploiting an observed high affinity of the compound for pancreatic ductal adenocarcinoma and other tumors. The molecule has shown signals of tumor growth inhibition in clinical studies of US and Australian metastatic pancreatic cancer patients, demonstrating a median overall survival (OS) of 14.6 months which is final, and an objective response rate (ORR) of 48%, both exceeding what is seen typically with the standard of care of gemcitabine + nab-paclitaxel suggesting potential complementary activity with the existing FDA-approved standard chemotherapy regimen. In data evaluated from clinical studies to date, SBP-101 has not shown exacerbation of bone marrow suppression and peripheral neuropathy, which can be chemotherapy-related adverse events. Serious visual adverse events have been evaluated and patients with a history of retinopathy or at risk of retinal detachment will be excluded from future SBP-101 studies. The safety data and PMI profile observed in the current Panbela sponsored clinical trial provides support for continued evaluation of SBP-101 in a randomized clinical trial. For more information, please visit View Source .

Flynpovi

Flynpovi is a combination of CPP-1X (eflornithine) and sulindac with a dual mechanism inhibiting polyamine synthesis and increase polyamine export and catabolism. In a Phase 3 clinical trial in patients with sporadic large bowel polyps, the combination prevented > 90% subsequent pre-cancerous sporadic adenomas versus placebo. Focusing on FAP patients with lower gastrointestinal tract anatomy in the recent Phase 3 trial comparing Flynpovi to single agent eflornithine and single agent sulindac, FAP patients with lower GI anatomy (patients with an intact colon, retained rectum or surgical pouch), Flynpovi showed statistically significant benefit compared to both single agents (p≤0.02) in delaying surgical events in the lower GI for up to four years. The safety profile for Flynpovi did not significantly differ from the single agents and supports the continued evaluation of Flynpovi for FAP.

CPP-1X

CPP-1X (eflornithine) is being developed as a single agent tablet or high dose power sachet for several indications including prevention of gastric cancer, treatment of neuroblastoma and recent onset Type 1 diabetes. Preclinical studies as well as Phase 1 or Phase 2 investigator-initiated trials suggest that CPP-1X treatment is well tolerated and has potential activity.

On August 4, 2022 PTC Therapeutics, Inc. (NASDAQ: PTCT) reported a corporate update and financial results for the second quarter ending June 30, 2022 (Press release, PTC Therapeutics, AUG 4, 2022, View Source [SID1234617534]).

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"We made significant progress in the second quarter toward achieving our ambitious goals for 2022. We continued to generate strong revenue growth, to expand our product portfolio, and to advance our pipeline," said Stuart W. Peltz, Ph.D., Chief Executive Officer, PTC Therapeutics, Inc. "PTC has a broad and deep pipeline across a range of diseases, and we eagerly anticipate important results for several registration-directed studies during the next six to twelve months and this will continue our transformational growth."

Key Corporate Updates:

The Duchenne muscular dystrophy (DMD) franchise continued to show strong growth, with second quarter total net product revenue of $134 million, or 32% year-over-year growth.
Translarna total net product revenue increased 46% year-over-year to $77 million, with growth coming from new patients in existing geographies and continued geographic expansion.
Emflaza total net product revenue grew 16% year-over-year to $57 million, driven by new patient starts, broader access, continued high compliance and appropriate weight-based dosing.
The FDA approved a label extension for Evrysdi (risdiplam) to include infants under 2 months old with SMA. Evrysdi is a product of the SMA collaboration among PTC, the SMA Foundation and Roche.
In July 2022, Upstaza (eladocagene exuparvovec), our gene therapy for AADC deficiency, received marketing authorization by the European Commission.
First group purchase order for Tegsedi in Brazil was fulfilled.
Key Clinical/Regulatory Updates:

PTC recently announced positive topline results of the placebo-controlled portion of Study 041 for Translarna. The Study 041 results add to the totality of evidence demonstrating the clinical benefit of Translarna.
PTC will update topline results of FITE-19 study of emvododstat for COVID-19 on second quarter call.
PTC continues to make progress in additional ongoing clinical studies:
The APHENITY Phase 3 trial of PTC923 for PKU, with results anticipated by the end of 2022.
The PIVOT-HD Phase 2 trial of PTC518 for Huntington’s disease, with data from the first 12 weeks of the placebo-controlled trial anticipated by the end of 2022.
The MIT-E Phase 2/3 vatiquinone trial for mitochondrial disease associated seizures, with results anticipated in the first quarter of 2023.
The MOVE-FA Phase 3 vatiquinone trial for Friedreich ataxia, with results anticipated in the second quarter of 2023.
Second Quarter 2022 Financial Highlights:

Total revenues were $165.5 million for the second quarter of 2022, compared to $116.7 million for the second quarter of 2021.
Total revenue includes net product revenue across the commercial portfolio of $143.7 million for the second quarter of 2022, compared to $103.1 million for the second quarter of 2021. Total revenue also includes royalty revenue of $21.8 million in the second quarter of 2022, compared to $13.6 million for the second quarter of 2021.
Translarna net product revenues were $77.0 million for the second quarter of 2022, compared to $52.6 million for the second quarter of 2021. These results reflect an increase in net product sales coming from new patients in existing geographies and continued geographic expansion.
Emflaza net product revenues were $56.8 million for the second quarter of 2022, compared to $49.1 million for the second quarter of 2021. These results reflect new patient starts, broader access, continued high compliance, and appropriate weight-based dosing.
Roche reported year to date 2022 Evrysdi sales of approximately CHF 500 million, resulting in royalty revenue of $21.8 million to PTC in the second quarter of 2022, as compared to $13.6 million for the second quarter of 2021.
Based on U.S. GAAP (Generally Accepted Accounting Principles), GAAP R&D expenses were $157.3 million for the second quarter of 2022, compared to $125.5 million for the second quarter of 2021. The increase reflects increased investment in research programs and advancement of the clinical pipeline.
Non-GAAP R&D expenses were $143.5 million for the second quarter of 2022, excluding $13.8 million in non-cash, stock-based compensation expense, compared to $112.0 million for the second quarter of 2021, excluding $13.4 million in non-cash, stock-based compensation expense.
GAAP SG&A expenses were $79.9 million for the second quarter of 2022, compared to $68.9 million for the second quarter of 2021. The increase reflects our continued investment to support commercial activities including our expanding commercial portfolio.
Non-GAAP SG&A expenses were $66.0 million for the second quarter of 2022, excluding $13.9 million in non-cash, stock-based compensation expense, compared to $56.6 million for the second quarter of 2021, excluding $12.3 million in non-cash, stock-based compensation expense.
Change in the fair value of deferred and contingent consideration was a $15.2 million gain for the second quarter of 2022, compared to a $0.7 million loss for the second quarter of 2021. The change in fair value of deferred and contingent consideration is related to the fair valuation of potential future consideration to be paid to former equity holders of Agilis Biotherapeutics, Inc. (Agilis) in connection with PTC’s acquisition of Agilis, which closed in August 2018.
Net loss was $152.1 million for the second quarter of 2022, compared to net loss of $118.4 million for the second quarter of 2021.
Cash, cash equivalents, and marketable securities was $505.5 million on June 30, 2022, compared to $773.4 million at December 31, 2021.
Shares issued and outstanding as of June 30, 2022 were 71,505,889.
PTC Reaffirms Full Year 2022 Financial Guidance:

PTC anticipates total revenues for the full year 2022 to be between $700 and $750 million.
PTC anticipates net product revenues for the DMD franchise for the full year 2022 to be between $475 and $495 million.
PTC anticipates GAAP R&D and SG&A expense for the full year 2022 to be between $915 and $965 million.
PTC anticipates Non-GAAP R&D and SG&A expense for the full year 2022 to be between $800 and $850 million, excluding estimated non-cash, stock-based compensation expense of $115 million.
Non-GAAP Financial Measures:

In this press release, the financial results of PTC are provided in accordance with GAAP and using certain non-GAAP financial measures. In particular, the non-GAAP financial measures exclude non-cash, stock-based compensation expense. These non-GAAP financial measures are provided as a complement to financial measures reported in GAAP because management uses these non-GAAP financial measures when assessing and identifying operational trends. In management’s opinion, these non-GAAP financial measures are useful to investors and other users of PTC’s financial statements by providing greater transparency into the historical and projected operating performance of PTC and the company’s future outlook. Non-GAAP financial measures are not an alternative for financial measures prepared in accordance with GAAP. Quantitative reconciliations of the non-GAAP financial measures to their respective closest equivalent GAAP financial measures are included in the table below.

Today’s Conference Call and Webcast Reminder:

To access the call by phone, please click here to register and you will be provided with dial-in details. To avoid delays, we recommend participants dial in to the conference call 15 minutes prior to the start of the call. The webcast conference call can be accessed on the Investor section of the PTC website at View Source A replay of the call will be available approximately two hours after completion of the call and will be archived on the company’s website for 30 days following the call.