On August 19, 2021 Medivir AB reported that Interim Report January – June 2021 (Press release, Medivir, AUG 19, 2021, View Source;interim-report-january–june-2021-301358672.html [SID1234586772])

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

April – June
Financial summary for the quarter

Net turnover amounted to SEK 0.9 (4.0) million.
The loss before interest, tax, depreciation and amortization (EBITDA) amounted to SEK -17.1 (-12.4) million. Basic and diluted earnings per share amounted to SEK -0.35 (-0.52) and SEK -0.35 (-0.52) respectively.
Cash flow from operating activities amounted to SEK -21.9 (-23.3) million.
Liquid assets and short-term investments at the end of the period amounted to SEK 247.8 (94.9) million.
Significant events during the quarter

On April 16, it was announced that Magnus Christensen had been appointed interim CEO of Medivir. He took up his new role in connection with Medivir’s AGM on May 5, 2021.
On April 19, it was announced that the overall results from the first part of the phase Ib study with MIV-818 were positive with a good safety and tolerability profile. Thus, the starting dose for the second part of the phase Ib study could be determined.
In May, positive results from an investigator-initiated phase II clinical study of remetinostat in patients with squamous cell carcinoma (SCC) were released on clinicaltrials.gov.
In May, the design for the upcoming phase 1b/2a combination study with the company’s leading candidate drug, MIV-818 against liver cancer, was presented. In the study, MIV-818 will be administered in two combinations, with either lenvatinib, a tyrosine kinase inhibitor, or pembrolizumab, an anti-PD-1 checkpoint inhibitor.
January – June
Financial summary for the period

Net turnover amounted to SEK 10.8 (11.4) million.
The loss before interest, tax, depreciation and amortization (EBITDA) amounted to SEK -24.3 (-33.1) million. Basic and diluted earnings per share amounted to SEK -0.57 (-1.49) and SEK -0.57 (-1.49) respectively.
Cash flow from operating activities amounted to SEK -23.3 (-40.0) million.
Liquid assets and short-term investments at the end of the period amounted to SEK 247.8 (94.9) million.
Significant events after the end of the period

In July, Malene Jensen was appointed Vice President Clinical Development. She will assume her role on September 6, 2021.
In August, it was announced that data from the MIV-818 phase 1b study will be presented at the ESMO (Free ESMO Whitepaper) Congress in September.
In August, the positive results from the phase II study with remetinostat against basal cell carcinoma were published in the scientific journal Clinical Cancer Research.
In August, it was announced that Medivir, through a renegotiated multi-party agreement, strengthens the business development potential for remetinostat.
Conference call for investors, analysts and the media
The Interim Report January – June 2021 will be presented by Medivir’s interim CEO, Magnus Christensen.

The conference call will also be streamed via a link on the website: www.medivir.com
The presentation will be available on Medivir’s website after completion of the conference.

CEO’s message
The clinical development of MIV-818 remains in focus. Positive topline results in the phase 1b monotherapy study. The design determined for the phase 1b/2a combination study in the clinical MIV-818 program.

Medivir’s central task is to advance the clinical program for our leading candidate drug MIV-818, which has the potential to be a liver-directed, orally administered drug that can help patients with various cancers of the liver. This work has also characterized our operations also in the past quarter.

In April we were able to announce that the results from the first part of the phase 1b study with MIV-818 were positive with a good safety and tolerability profile. Thereby, we were also able to determine the starting dose for the second part of the study, where we combine MIV-818 with standard treatment. Data from the first part of the phase 1b study will be presented at the ESMO (Free ESMO Whitepaper) scientific conference in September.

Due to its unique mechanism of action, MIV-818 is attractive to combine with a multitude of other drugs for the treatment of hepatocellular carcinoma (HCC). We have been working on refining the design for the next step in the clinical program, the upcoming phase 1b/2a combination study with MIV-818, and at the end of May we presented how the study is structured. MIV-818 will be administered in two combinations, either with lenvatinib, a tyrosine kinase inhibitor, or with pembrolizumab, an anti-PD-1 checkpoint inhibitor.

The study is an open-label, multi-center phase 1b/2a study that begins with a dose escalation part to determine the recommended phase 2 dose (RP2D). This is followed by the expansion study (phase 2a) with an initial evaluation of the safety and efficacy of the combinations of MIV-818 with lenvatinib or pembrolizumab. The study will include patients with HCC who have progressed on, or are intolerant of, first line standard therapy.

We plan to recruit the first patient for the combination study in the second half of 2021. However, we cannot guarantee that the Covid-19 pandemic will not affect our schedule.

MIV-818 is proprietary and wholly owned by Medivir, i.e. we do not have to pay any future milestones or royalties to any third party.

We have two more drug development projects in the clinical development phase, remetinostat, and MIV-711. Medivir does not conduct clinical development of these projects on its own, but instead seeks partners for further development.

During the quarter, positive results were published from an investigator-initiated clinical phase II study of remetinostat in patients with squamous cell carcinoma (SCC). The study was conducted at the Stanford University School of Medicine in California, USA. The primary objective of the study was to assess the effects of topical remetinostat on biopsy-proven SCC and SCC in situ tumors. In August, the positive results from the phase II study with remetinostat in patients with BCC were also published in the scientific journal Clinical Cancer Research.

The results are very promising and provide further support for the potential of remetinostat as a treatment for a number of skin-associated cancers in addition to cutaneous T-cell lymphoma (CTCL). Medivir renegotiated in August a multi-party agreement with the originators of remetinostat and TetraLogic Pharmaceuticals Corporation and The Leukemia & Lymphoma Society regarding the financial obligations for remetinostat in order to create better conditions for business development.

Medivir’s birinapant project, for the treatment of solid tumors, was outlicensed to the American company IGM Biosciences at the beginning of the year. IGM has the global and exclusive rights to develop birinapant. According to IGM’s Q2 report, they plan to initiate clinical trials with birinapant in combination with their proprietary antibody IGM-8444 during 2021.

At Medivir’s AGM on May 5, former CEO Yilmaz Mahshid was elected new board member and Uli Hacksell was elected chairman of the board. This guarantee continued scientific vitality and business acumen in the Board’s work.

In July, Malene Jensen was recruited as Vice President Clinical Development and a member of the company’s management team. With extensive experience in clinical development, Malene will focus on the clinical studies with MIV-818.

I am really impressed by the determination and dedication shared by all Medivir employees. The goal is to develop an effective drug against liver cancer through MIV-818. Given that this work continues to show good results, it could make a big difference for patients and for healthcare and thus also for the company’s shareholders.

On August 19, 2021 NeoDynamics reported that Interim report Jan-June 2021 (Press release, NeoDynamics, AUG 19, 2021, View Source [SID1234586771])

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Second Quarter 2021

Revenue amounted to SEK 411 (6,263) thousand, of which SEK 383 (5,787) thousand were capitalized costs.
Loss after tax amounted to SEK-18,263 (-5,516) thousand.
Loss per share SEK -0.30 (-0.18).
Cash and cash equivalents amounted to SEK 48,339 (7,177) thousand.
First half of 2021

Revenues amounted to SEK 816 (12,531) thousand, of which SEK 762 (12,090) thousand capitalized costs.
Cash flow from operating activities amounted to SEK -23,999 (-13,107) thousand.
Profit after tax amounted to SEK -35,519 (-12,751) thousand.
Earnings per share amounted to SEK -0.59 (-0.53).
The equity ratio was 95 (94) percent.
Significant events during the quarter

NeoDynamics presented a scientific abstract at the annual surgery conference ABS, Association of Breast Surgeons, in Birmingham, which describes how the company’s FlexiPulse needle surpasses standard biopsy in preclinical models by almost 300 percent in terms of volume.
The Annual General Meeting re-elected the Board members Carina Bolin, Claes Pettersson, Ingrid Salén, Jie Bao and Xiao-Jun Xu, and appointed Matthey E. Colpoys Jr. as a new Board member.
At mid-year, about 30 clinics with radiology teams in Sweden, the United Kingdom, Germany and other German-speaking countries in Europe had had workshops with the biopsy system NeoNavia.
Significant events after period-end

Hermann-Josef-Hospital in Erkelenz, a university hospital within the University of Aachen, became the first German hospital to order NeoNavia.
CEO comment

Clinics build experience

We continue to introduce the biopsy system NeoNavia in clinics in our markets in Europe. The pandemic has made traditional and effective launch methods impossible, which means introducing the product to doctors at congresses and trade fairs, in parallel with building experience through workshops and thereby reaching out more quickly. Instead, NeoDynamics has been forced to rely on individual hospital meetings with workshops where doctors are given the opportunity to test the product and train in how it is used.

The challenge with this procedure during the spring has been to get permission to be at the clinic. On a few occasions, smaller workshops have been held outside the hospitals. Once these workshops are completed, a majority of clinics want to use the product in regular operation for 2-3 months to see how it fits in and let the whole team of the hospital’s radiologists, or as in Germany gynecologists, get used to handling NeoNavia in clinical everyday life. In dialogue with the clinic, the hospital’s purchasing department is involved in designing a quote and qualifying NeoDynamics as a supplier. Only then can NeoDynamics expect an order for the product. The process takes time and varies between clinics. By mid-year, the team had conducted about 30 workshops.

First in Germany to place an order was the reputable breast center at Hermann-Josef-Hospital in Erkelenz, Germany, which belongs to the University Hospital of Aachen, which participated in the PULSE study and which also serves as a reference center. We expect to recruit more reference centers in different countries to pave the way for the majority of the clinics that have tried the product to also adopt the technology and submit orders during the latter part of 2021.

The team continues to arrange workshops with specialists and in the autumn, several conferences once again welcome participants to participate physically. The first conference we plan to attend on site is the Schweizerische Gesellschaft fur Senology, which will be held in Basel on September 8-9 to be followed by two further congresses in September and October for the German-speaking part of the country. A very positive sign which means that we in Europe are gradually beginning to return to a more normal market situation.

Publications create interest

Another important way to present NeoNavia to physicians is to present peer reviewed abstracts from our clinical program through various types of scientific conferences. Getting an abstract selected for presentation is a measure of the scientific level we hold in our study program – and of course a way to make NeoNavia known.

During the second quarter, NeoNavia was exposed in this way at the prestigious annual British Breast Surgery Congress, ABS. NeoDynamics continues the work of documenting the product through its clinical program and more scientific abstracts are expected this year. The work of course facilitates the dialogue with doctors, at the same time as it is also a part of creating interest in NeoNavia among potential partners.

United States the next major milestone

In the United States, work continues on compiling the registration application to be able to submit it to the US Food and Drug Administration FDA in the fall. We have a dialogue with the authority, which also communicates that their response times are longer than normal as a result of a large part of the authority’s resources being redirected to matters related to Covid-19. With a well-prepared application, however, the need for interaction with the authority after the file has been submitted decreases. The team’s ambition is to achieve an application of high quality through underhand dialogue with the FDA. A registration of the product in the USA is an important milestone for both NeoDynamics and NeoNavia as it is an important stamp of quality that also opens up a significant new market. It is also expected to lead to a significantly more concrete interest from potential partners.

During the quarter, NeoDynamics strengthened its expertise in the important US market through the election of Matt Colpoys to the Board. Matt adds valuable knowledge about both the market and potential partners. The pieces are thus beginning to come into place for NeoDynamics to be able to add the USA as a market.

On August 19, 2021 Compugen Ltd. (NASDAQ: CGEN), a leader in predictive discovery and development of first-in-class therapeutics for cancer immunotherapy, reported that a bispecific antibody of AstraZeneca derived from COM902, Compugen’s high affinity anti-TIGIT antibody, will advance into clinical development (Press release, Compugen, AUG 19, 2021, View Source [SID1234586770]). AstraZeneca (LSE/STO/Nasdaq: AZN) plans to initiate a Phase 1/2 study evaluating AZD2936, a TIGIT/PD-1 bispecific antibody, in patients with advanced or metastatic non-small cell lung cancer.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

COM902 was licensed to AstraZeneca in 2018 exclusively for the development of bispecific and multi-specific antibody products, with AstraZeneca responsible for all research, development, and commercial activities. Compugen retains all other rights to the program with exception to those licensed to AstraZeneca.

"The advancement into the clinic of this bispecific derived from COM902 provides additional support for COM902’s therapeutic potential by a global leader in the development of antibody-based oncology therapeutics," said Anat Cohen-Dayag, Ph.D., President and Chief Executive Officer of Compugen. "We believe COM902’s properties, including its high affinity and superior binding compared to other anti-TIGITs tested in a preclinical setting, were key attributes that contributed to the decision to obtain rights for the development of bispecific products and further advancement of AZD2936 to the clinic. The exclusive license agreement with AstraZeneca allows us to broaden our product opportunities and specifically capitalize on bispecific products while maintaining ownership of COM902 for the development of various combination therapies in general, and DNAM-axis related specifically, including in combination with COM701 our first in class anti-PVRIG antibody. We are excited to disclose the identity of our program licensed to AstraZeneca and we look forward to reporting future milestone payments as they occur"

About the Compugen-AstraZeneca License Agreement

In 2018, Compugen and AstraZeneca entered into an agreement by which Compugen provided an exclusive license to AstraZeneca for the development of bispecific and multi-specific antibody products derived from Compugen’s monospecific antibodies that bind to TIGIT, including COM902, with AstraZeneca responsible for all research, development, and commercial activities. AstraZeneca has the right to create multiple products under this license. Compugen has received a $10 million upfront payment and an additional $2 million milestone payment to date, out of up to an aggregate milestone amount of $200 million that the Company is eligible to receive in development, regulatory and commercial milestones for the first product, as well as tiered royalties on future product sales. If additional products are developed, additional milestones and royalties would be due to Compugen. Under the terms of the license agreement, Compugen retained all other rights to its entire pipeline of programs as monotherapies and in combination with other products.

About the Study

Details are available on ClinicalTrials.gov, identifier: NCT04995523

About COM902

COM902 is a high affinity, fully human antibody that blocks the interaction of TIGIT with PVR, its ligand, and consequently enhances T cell function. Data suggests that COM902 has in vitro activity comparable or superior to TIGIT antibodies in clinical development. It is currently being evaluated by the Company in a Phase 1 clinical studies in patients with advanced malignancies who have exhausted all available standard therapies. Compugen has demonstrated in preclinical studies that simultaneous inhibition of TIGIT and PVRIG, the two coinhibitory arms of the DNAM axis, can increase antitumor immune responses, which may be further enhanced with the addition of PD-1 blockade. These data suggest that treatment with COM701 and COM902, targeting PVRIG and TIGIT, respectively, alone or in combination with a PD-1 inhibitor, has the potential to expand immuno-oncology treatment to patient populations who are non-responsive or refractory to existing immunotherapies. The discovery of TIGIT, using the Company’s computational discovery platform, was published by Compugen in October 2009 in the Proceedings of the National Academy of Sciences (PNAS).

On August 19, 2021 AffyImmune Therapeutics, Inc., a clinical stage biotechnology company finding safe, effective ways to use CAR T cells against solid cancers, reported that scientific co-founder Moonsoo Jin will present twice at Hanson Wade’s 6th CAR-TCR Summit being held virtually August 30 – September 2 (Press release, AffyImmune Therapeutics, AUG 19, 2021, View Source [SID1234586769]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Dr. Jin’s first presentation "Developing Manufacturing and Quality Control Platforms for Cell Immunotherapy" will occur as part of the CAR-TCR 101 Deep Dive Day Bootcamp at 1:30 pm EST on August 30. In this talk, he will explore strategies to optimize CMC for high quality cell production, summarize key quality control parameters and assays, and discuss how to build product development teams to effectively manage change controls and scale.

His second presentation "First in Patient Clinical Readouts for Affinity Tuned CAR T with Real-Time Monitoring of Response" is part of the Clinical Management track on September 1 at 2:30 pm EST. There, Dr. Jin will expand on AffyImmune’s Tune & Track platform, including early insights into clinical experiences and results.

"We are honored to have two speaking slots at this year’s CAR-TCR conference," began Eric von Hofe, President of AffyImmune. "With these presentations, AffyImmune will demonstrate its technological and clinical advancements from the past year, particularly with our Tune & Track platform."

Interested parties can register at https://car-tcr-summit.com/take-part/register.

On August 19, 2021 The Janssen Pharmaceutical Companies of Johnson & Johnson reported preliminary data from the Phase 1 CHRYSALIS study evaluating RYBREVANTTM (amivantamab-vmjw) for the treatment of patients with non-small cell lung cancer (NSCLC) with mesenchymal-epithelial transition (MET) exon 14 skipping (METex14) mutations (Press release, Johnson & Johnson, AUG 19, 2021, View Source [SID1234586768]). The initial data showed anti-tumor activity in patients with METex14 mutations and a safety profile consistent with reported experience at the approved CHRYSALIS Phase 2 dose (RYBREVANTTM 1050 mg [<80 kg] / 1400 mg [≥80 kg]).1 These findings will be featured at the virtual International Association for the Study of Lung Cancer’s (IASLC) 2021 World Conference on Lung Cancer (WCLC) taking place from September 8-14 in Denver as an oral presentation (Abstract #OA15.03).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

METex14 mutations are found in approximately three percent of patients with NSCLC.2 These genetic alterations result in hyperactivation of the MET receptor with corresponding cancer cell growth.3 While MET inhibitors have recently received accelerated approval in this setting in some regions, the vast majority of patients eventually acquire resistance to these therapies, thus underscoring the need for new treatment options.4,5,6

"Newer treatment advances for non-small cell lung cancer provide benefit to patients with MET exon 14 skipping mutations, but because they are effective for only a finite period of time, patients ultimately find themselves in need of new therapies," said Alexander Spira, M.D., Ph.D., FACP, Director of the Virginia Cancer Specialists Research Institute, Co-Chair U.S. Oncology Thoracic Program and presenting study investigator†. "We look forward to sharing these latest results for amivantamab that suggest its novel mechanism of action may be of benefit to people living with this type of lung cancer."

In the METex14 cohort of the Phase 1 CHRYSALIS study, 19 patients with this genetic alteration received intravenous RYBREVANTTM 1050 mg (for patients who weigh <80 kg) or 1400 mg (for patients who weigh ≥80 kg).1 Disease response was evaluated using overall response rate (ORR), per Response Evaluation Criteria in Solid Tumors Version 1.1* (RECIST v1.1) as the primary endpoint.1 Of the 14 response-evaluable patients, partial responses were observed in 64 percent with four patients pending confirmation.1 Activity was observed in treatment-naïve and previously-treated patients, including four of seven patients previously treated with MET tyrosine kinase inhibitors (TKIs).1 The median time to first response was 4.1 months (range, 1.6–9.9).1

The majority of treatment-related adverse events (AEs) were Grade 1-2.1 Treatment-related Grade ≥3 AEs were observed in three patients (16 percent), which included dyspnea (N=1), hypoalbuminemia (N=1) and rash (N=1).1 The incidence of treatment-related AEs leading to dose reduction and discontinuation was 11 percent and five percent, respectively.1 Dose interruptions occurred in 32 percent of patients.1

In May 2021, RYBREVANTTM received U.S. Food and Drug Administration (FDA) approval for patients with locally advanced or metastatic NSCLC with epidermal growth factor receptor (EGFR) exon 20 insertion mutations, based on data showing an ORR of 40 percent (95 percent CI, 29 – 51) and median duration of response of 11.1 months (95 percent CI, 6.9 – NE).7

"While the recent FDA approval of RYBREVANT was an important milestone for patients with non-small cell lung cancer with EGFR exon 20 insertion mutations, there continues to be a lack of long-term treatment options for patients with other mutations, including MET exon 14 skipping mutations," said Kiran Patel, M.D., Vice President, Clinical Development, Solid Tumors, Janssen Research & Development, LLC. "We are encouraged by these data showing evidence that RYBREVANTTM can lead to broad activity against both EGFR and MET-driven tumors."

About RYBREVANTTM
RYBREVANTTM (amivantamab-vmjw) received accelerated approval by the U.S. FDA for the treatment of adult patients with locally advanced or metastatic NSCLC with EGFR exon 20 insertion mutations, as detected by an FDA-approved test, whose disease has progressed on or after platinum-based chemotherapy in May 2021.7 Janssen has filed regulatory submissions for RYBREVANTTM with health authorities in Europe and other markets. RYBREVANTTM is being studied in multiple clinical trials, including a Phase 1/1b study, CHRYSALIS-2 (NCT04077463) to examine the combination in patients who have progressed after treatment with osimertinib and chemotherapy; as first-line therapy in untreated advanced EGFR-mutated NSCLC in the Phase 3 MARIPOSA (NCT04487080) study assessing amivantamab in combination with lazertinib**; the planned Phase 3 MARIPOSA-2 (NCT04988295) study assessing the efficacy of lazertinib, amivantamab, carboplatin-pemetrexed vs. with carboplatin-pemetrexed in patients with locally advanced or metastatic EGFR exon 19 deletion or exon 21 L858R substitution NSCLC after osimertinib failure; the Phase 3 PAPILLON (NCT04538664) study assessing RYBREVANTTM in combination with carboplatin-pemetrexed for patients with advanced or metastatic EGFR-mutated NSCLC and exon 20 insertion mutations; and the Phase 1 PALOMA (NCT04606381) study assessing the feasibility of subcutaneous (SC) administration of RYBREVANTTM based on safety and pharmacokinetics and to determine a dose, dose regimen and formulation for RYBREVANTTM SC delivery.8,9,10,11,12

**In 2018, Janssen Biotech, Inc. entered into a license and collaboration agreement with Yuhan Corporation for the development of lazertinib.

About the CHRYSALIS Study
CHRYSALIS (NCT02609776) is a Phase 1 open-label, multicenter, first-in-human study to evaluate the safety, pharmacokinetics and preliminary efficacy of RYBREVANTTM as a monotherapy and in combinations including with lazertinib, a novel third-generation EGFR TKI13, in adults with advanced NSCLC.12 The study consists of two parts: RYBREVANTTM monotherapy and combination-dose escalations and RYBREVANTTM monotherapy and combination-dose expansions.12

About Non-Small Cell Lung Cancer (NSCLC)
Worldwide, lung cancer is one of the most common cancers, and NSCLC makes up 80 to 85 percent of all lung cancers.14,15 The main subtypes of NSCLC are adenocarcinoma, squamous cell carcinoma and large cell carcinoma.16 Among the most common driver mutations in NSCLC are alterations in EGFR, which is a receptor tyrosine kinase supporting cell growth and division.16 EGFR mutations are present in 10 to 15 percent17,18,19,20,21 of people with NSCLC adenocarcinoma and occur in 40 to 50 percent of Asians.22,23 METex14 mutations are found in approximately three percent of patients with NSCLC.2

RYBREVANT IMPORTANT SAFETY INFORMATION7

WARNINGS AND PRECAUTIONS

Infusion Related Reactions7
RYBREVANT can cause infusion related reactions (IRR); signs and symptoms of IRR include dyspnea, flushing, fever, chills, nausea, chest discomfort, hypotension, and vomiting.

Based on the safety population, IRR occurred in 66% of patients treated with RYBREVANT. Among patients receiving treatment on Week 1 Day 1, 65% experienced an IRR, while the incidence of IRR was 3.4% with the Day 2 infusion, 0.4% with the Week 2 infusion, and cumulatively 1.1% with subsequent infusions. Of the reported IRRs, 97% were Grade 1-2, 2.2% were Grade 3, and 0.4% were Grade 4. The median time to onset was 1 hour (range 0.1 to 18 hours) after start of infusion. The incidence of infusion modifications due to IRR was 62% and 1.3% of patients permanently discontinued RYBREVANT due to IRR.

Premedicate with antihistamines, antipyretics, and glucocorticoids and infuse RYBREVANT as recommended. Administer RYBREVANT via a peripheral line on Week 1 and Week 2. Monitor patients for any signs and symptoms of infusion reactions during RYBREVANT infusion in a setting where cardiopulmonary resuscitation medication and equipment are available. Interrupt infusion if IRR is suspected. Reduce the infusion rate or permanently discontinue RYBREVANT based on severity.

Interstitial Lung Disease/Pneumonitis7
RYBREVANT can cause interstitial lung disease (ILD)/pneumonitis. Based on the safety population, ILD/pneumonitis occurred in 3.3% of patients treated with RYBREVANT, with 0.7% of patients experiencing Grade 3 ILD/pneumonitis. Three patients (1%) discontinued RYBREVANT due to ILD/pneumonitis.

Monitor patients for new or worsening symptoms indicative of ILD/pneumonitis (e.g., dyspnea, cough, fever). Immediately withhold RYBREVANT in patients with suspected ILD/pneumonitis and permanently discontinue if ILD/pneumonitis is confirmed.

Dermatologic Adverse Reactions7
RYBREVANT can cause rash (including dermatitis acneiform), pruritus and dry skin. Based on the safety population, rash occurred in 74% of patients treated with RYBREVANT, including Grade 3 rash in 3.3% of patients. The median time to onset of rash was 14 days (range: 1 to 276 days). Rash leading to dose reduction occurred in 5% of patients, and RYBREVANT was permanently discontinued due to rash in 0.7% of patients.

Toxic epidermal necrolysis occurred in one patient (0.3%) treated with RYBREVANT.

Instruct patients to limit sun exposure during and for 2 months after treatment with RYBREVANT. Advise patients to wear protective clothing and use broad spectrum UVA/UVB sunscreen. Alcohol free emollient cream is recommended for dry skin.

If skin reactions develop, start topical corticosteroids and topical and/or oral antibiotics. For Grade 3 reactions, add oral steroids and consider dermatologic consultation. Promptly refer patients presenting with severe rash, atypical appearance or distribution, or lack of improvement within 2 weeks to a dermatologist. Withhold, dose reduce or permanently discontinue RYBREVANT based on severity.

Ocular Toxicity7
RYBREVANT can cause ocular toxicity including keratitis, dry eye symptoms, conjunctival redness, blurred vision, visual impairment, ocular itching, and uveitis. Based on the safety population, keratitis occurred in 0.7% and uveitis occurred in 0.3% of patients treated with RYBREVANT. All events were Grade 1-2. Promptly refer patients presenting with eye symptoms to an ophthalmologist. Withhold, dose reduce or permanently discontinue RYBREVANT based on severity.

Embryo Fetal Toxicity7
Based on its mechanism of action and findings from animal models, RYBREVANT can cause fetal harm when administered to a pregnant woman. Advise females of reproductive potential of the potential risk to the fetus. Advise female patients of reproductive potential to use effective contraception during treatment and for 3 months after the final dose of RYBREVANT.

Adverse Reactions7
The most common adverse reactions (≥20%) were rash, IRR, paronychia, musculoskeletal pain, dyspnea, nausea, fatigue, edema, stomatitis, cough, constipation, and vomiting. The most common Grade 3 or 4 laboratory abnormalities (≥2%) were decreased lymphocytes, decreased albumin, decreased phosphate, decreased potassium, increased alkaline phosphatase, increased glucose, increased gamma-glutamyl transferase, and decreased sodium.