Knight Therapeutics Announces Health Canada Approval for NERLYNX® to Treat HER2-Positive Metastatic Breast Cancer

Knight Therapeutics Inc. (TSX: GUD), ("Knight") a pan-American (ex-USA) specialty pharmaceutical company, announced today that Health Canada has approved NERLYNX® (neratinib) in combination with capecitabine for the treatment of adult patients with metastatic HER2-overexpressedamplified breast cancer, who have received two or more prior anti-HER2-based regimens in the metastatic setting. The approval was based on results of the global Phase III NALA trial. Knight has the exclusive right to commercialize NERLYNX® in Canada under the terms of a license agreement entered into with Puma Biotechnology, Inc. (NASDAQ: PBYI).

According to Canadian Cancer Statistics, breast cancer accounts for one-quarter (25%) of all new cancer cases in women ² . Approximately 27,700 women were diagnosed with breast cancer in 2020, and 5,100 died of the disease in the same year ² . Studies show that up to 20% of breast cancer tumors have an over-expression of the HER2 protein. Women with breast cancer that over-expresses HER2, referred to as HER2-positive breast cancer, are at greater risk for disease progression and death than women whose tumors do not over-express HER2. Although research has shown that trastuzumab can reduce the risk of early stage HER2-positive breast cancer recurring, up to 25% of treated patients experience recurrence within 10 years, the majority of which are metastatic recurrences ^{4 -5} .

"We are pleased to provide Canadian HER2-positive breast cancer patients and physicians with an effective medicine following previous treatment with other anti-HER2 agents in the metastatic setting," said Jody Engel, Country Manager Canada at Knight Therapeutics Inc. "This approval will add another indication to NERLYNX's current usage in extended adjuvant breast cancer."

About NERLYNX®

NERLYNX® is a potent irreversible tyrosine kinase inhibitor, or TKI, that blocks signal transduction through the human epidermal growth factor receptors, HER1, HER2 and HER4. On July 16, 2019, Health Canada approved NERLYNX® for the extended adjuvant treatment of women with early-stage hormone receptor positive, HER2-overexpressed/amplified breast cancer within one year after completion of trastuzumab-based adjuvant therapy ¹ . NERLYNX® is now covered by several private insurance companies in Canada.

About NALA

The efficacy of neratinib in combination with capecitabine was investigated in NALA ³ (NCT01808573), a randomized, multicenter, open-label, Phase III clinical trial in 621 patients with metastatic HER2-positive breast cancer who received two or more prior anti-HER2-based regimens in the metastatic setting.

The main efficacy outcome measures were progression-free survival (PFS) and overall survival (OS). Key secondary outcome measures were objective response rate (ORR) and duration of response (DOR). Treatment with neratinib in combination with capecitabine resulted in a statistically significant improvement in PFS (Hazard Ratio 0.76; 95% CI: 0.63, 0.93; p=0.0059) compared to treatment with lapatinib plus capecitabine. The PFS rate at 12 months was 29% (95% CI: 23, 35) for patients who received neratinib plus capecitabine vs 15% (95% CI: 10, 20) for patients who received lapatinib plus capecitabine; the PFS rate at 24 months was 12% (95% CI: 7, 18) vs 3% (95% CI: 1, 8), respectively.

Median OS was 21 months (95% CI: 17.7, 23.5) for patients who received neratinib in combination with capecitabine compared to 18.7 months (95% CI: 15.5, 21.2) for patients who received lapatinib in combination with capecitabine (HR 0.88; 95% CI: 0.72, 1.07; p=0.2086). The ORR was 32.8% (95% CI: 27.1, 38.9) vs 26.7% (95% CI: 21.5, 32.4), respectively. Median duration of response was 8.5 months (95% CI: 5.6, 11.2) vs 5.6 months (95% CI: 4.2, 6.4), respectively.   The most common adverse reactions of any grade (≥10%) in the neratinib plus capecitabine arm were diarrhea, nausea, palmar-plantar erythrodysaesthesia syndrome, vomiting, fatigue/asthenia, decreased appetite, constipation, stomatitis, weight decreased, rash, nail disorders, dizziness, back pain and arthralgia. Serious adverse reactions reported in ≥ 3 patients (1%) in the neratinib plus capecitabine arm included diarrhea, pleural effusion, vomiting, acute kidney injury, nausea, metastases to central nervous system, pneumonia, cellulitis, dehydration, seizure, constipation, pyrexia, and urinary tract infection.

The recommended neratinib dose for metastatic breast cancer is 240 mg (6 tablets) given orally once daily with food on days 1-21 of a 21-day cycle plus capecitabine (750 mg/m ² given orally twice daily) on days 1-14 of a 21-day cycle until disease progression or unacceptable toxicities.

About Knight Therapeutics Inc.

Knight Therapeutics Inc., headquartered in Montreal, Canada, is a specialty pharmaceutical company focused on acquiring or in-licensing and commercializing innovative pharmaceutical products for Canada and Latin America. Knight owns Biotoscana Investments S.A., a pan-Latin American specialty pharmaceutical company. Knight Therapeutics Inc.'s shares trade on TSX under the symbol GUD. For more information about Knight Therapeutics Inc., please visit the company's web site at www.gud-knight.com or www.sedar.com.

Forward-Looking Statements for Knight Therapeutics Inc.

This document contains forward-looking statements for Knight Therapeutics Inc. and its subsidiaries. These forward-looking statements, by their nature, necessarily involve risks and uncertainties that could cause actual results to differ materially from those contemplated by the forward-looking statements. Knight Therapeutics Inc. considers the assumptions on which these forward-looking statements are based to be reasonable at the time they were prepared but cautions the reader that these assumptions regarding future events, many of which are beyond the control of Knight Therapeutics Inc. and its subsidiaries, may ultimately prove to be incorrect. Factors and risks, which could cause actual results to differ materially from current expectations are discussed in Knight Therapeutics Inc.'s Annual Report and in Knight Therapeutics Inc.'s Annual Information Form for the year ended December 31, 2020 as filed on www.sedar.com. Knight Therapeutics Inc. disclaims any intention or obligation to update or revise any forward-looking statements whether because of new information or future events, except as required by law.

References

1. NERLYNX® (neratinib) tablets. Product Monograph, June 2021.
2. Canadian Cancer Statistics, 2020. Toronto, ON: Canadian Cancer Society; 2020. Available at: https://action.cancer.ca/en/research/cancer-statistics/canadian-cancer-statistics
3. Saura, C., Oliveira, M., Feng, Y. H., Dai, M. S., Chen, S. W., Hurvitz, S. A., ... & NALA Investigators. (2020). Neratinib plus capecitabine versus lapatinib plus capecitabine in HER2-positive metastatic breast cancer previously treated with≥ 2 HER2-directed regimens: phase III NALA trial. Journal of Clinical Oncology, 38 (27), 3138.
4. Perez, E. A., Romond, E. H., Suman, V. J., Jeong, J. H., Sledge, G., Geyer Jr, C. E., ... & Wolmark, N. (2014). Trastuzumab plus adjuvant chemotherapy for human epidermal growth factor receptor 2–positive breast cancer: planned joint analysis of overall survival from NSABP B-31 and NCCTG N9831 . Journal of Clinical Oncology , 32(33), 3744.
5. Goldhirsch, A., Gelber, R. D., Piccart-Gebhart, M. J., De Azambuja, E., Procter, M., Suter, T. M., ... & Herceptin Adjuvant (HERA) Trial Study Team. (2013). 2 years versus 1 year of adjuvant trastuzumab for HER2-positive breast cancer (HERA): an open-label, randomised controlled trial. The Lancet , 382(9897), 1021-1028.