On June 22, 2020 Xencor, Inc. (NASDAQ: XNCR), a clinical-stage biopharmaceutical company developing engineered monoclonal antibodies for the treatment of cancer and autoimmune diseases, reported the presentation of new preclinical data from three XmAb 2+1 bispecific antibody programs and its IL-12-Fc cytokine program during the second session of the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Virtual Annual Meeting (Press release, Xencor, JUN 22, 2020, View Source [SID1234561353]). Poster presentations and audio descriptions are available to registrants of the AACR (Free AACR Whitepaper) Virtual Annual Meeting.

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"Compared to many therapeutic targets for blood cancers like CD19 or CD20, which are generally restricted to specific cell populations, solid tumor targets often are expressed on a range of normal tissues, including critical organs, which can limit the therapeutic index for drug candidates," said John Desjarlais, Ph.D., senior vice president and chief scientific officer at Xencor. "The XmAb 2+1 bispecific antibody format has two domains that bind the tumor target, and this bivalent binding can preferentially bind tumor cells with high target expression, potentially sparing low-expression normal tissues. This selectivity and potency tuning of T-cell activation may provide for higher efficacy and tolerability compared to other bispecific antibody formats.

"We have also presented data from our IL-12-Fc cytokine program, which builds off of our prior work with IL-15 and IL-2. IL-12 is a potent immune signaling protein that can have a dramatic effect on shrinking tumors; however, prior clinical studies have demonstrated IL-12 to have a narrow therapeutic window, limiting potential response rates. We created an IL-12 Fc-fusion with reduced potency in order to improve tolerability, slow receptor-mediated clearance and prolong the molecule’s half-life," said Dr. Desjarlais.

XmAb 2+1 Bispecific Antibodies

Poster: 2286, "XmAb30819, an XmAb 2+1 ENPP3 x CD3 bispecific antibody for RCC, demonstrates safety and efficacy in in-vivo preclinical studies"
Poster: 5663, "Affinity tuned XmAb 2+1 PSMA x CD3 bispecific antibodies demonstrate selective activity in prostate cancer models"
Poster: 5654, "Affinity tuned XmAb 2+1 anti-mesothelin x anti-CD3 bispecific antibody induces selective T cell directed cell cytotoxicity of human ovarian cancer cells"
ENPP3, PSMA and MSLN are tumor-associated antigens associated with renal cell carcinoma (RCC), prostate cancer and ovarian cancer, respectively, but they are not restricted to tumors and exhibit base level expression on normal tissues. Xencor has expanded its T-cell redirecting CD3 class of bispecific antibodies to create an XmAb 2+1 bispecific antibody format, utilizing an engineered heterodimeric Fc domain, two identical tumor targeting domains and one CD3 targeting domain. The affinities for antigen binding are reduced, which allows for selective engagement of high antigen-expressing tumor cells over low antigen-expressing normal cells. In preclinical models, XmAb 2+1 bispecific antibodies bound preferentially to tumor cells compared to normal cells and effectively recruited T cells to kill tumor cells selectively. Additional data presented on XmAb 2+1 PSMA x CD3 bispecific antibody candidates and XmAb30819, a first-in-class XmAb 2+1 ENPP3 x CD3 bispecific antibody, demonstrated strong reversal of tumor growth in human-cell engrafted mouse models of disease. Further data presented from preclinical studies of XmAb30819 in non-human primates demonstrated it was well-tolerated with expected pharmacodynamics and an antibody-like half-life.

IL-12-Fc Cytokine

Poster: 5549, "Potency-reduced IL-12 heterodimeric Fc-fusions exhibit strong anti-tumor activity"
IL-12 is a heterodimeric proinflammatory cytokine produced by activated antigen-presenting cells, and it leads to proliferation of T cells and NK cells and increased cytotoxicity through high levels of interferon gamma signaling. IL-12-Fc fusions were engineered with potency-reduced IL-12 to improve its potential tolerability, slow receptor-mediated clearance and prolong its half-life in vivo. In preclinical models, these potency-reduced IL-12-Fc fusions demonstrated significant anti-tumor activity concurrent with activation and proliferation of CD8+ T cells, increased PD-1 checkpoint expression and increased levels of interferon gamma in serum. Anti-tumor activity was enhanced when combined with an anti-PD-1 antibody.

The posters will be archived under "Events & Presentations" in the Investors section of the Company’s website located at www.xencor.com.

On June 22, 2020 Sutro Biopharma, Inc. (NASDAQ: STRO), a clinical-stage drug discovery, development and manufacturing company focused on the application of precise protein engineering and rational design to create next-generation oncology therapeutics, reported the presentation of new preclinical data for its folate receptor alpha (FolRα) targeting antibody-drug conjugate, STRO-002, at the 2020 American Association for Cancer Research (AACR) (Free AACR Whitepaper) Virtual Annual Meeting II from June 22-24, 2020 (Press release, Sutro Biopharma, JUN 22, 2020, View Source;301080795.html [SID1234561369]). The data, being presented by Sutro’s Chief Scientific Officer, Trevor Hallam, Ph.D., demonstrates STRO-002’s immune-modulating properties and potentiation by PD-L1 blockade.

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The results of the study showed that in FolRα positive tumor cells, STRO-002 treatment induced hallmarks of immunogenic cell death, killing tumor cells while activating immune cells, including monocytes. When combined in mouse tumor models with avelumab, an anti-human & mouse PD-L1 monoclonal antibody, the combination treatment enhanced efficacy leading to more complete responses and increased killer T cells, than either agent alone. Importantly, the data suggest that a single dose of STRO-002 when combined with a PD-1/PD-L1 blockade could provide an effective and protective anti-tumor immune response.

"These data suggest that STRO-002 can drive immune-modulatory responses that can cause complete tumor regression, tumor specific T cell activation and adaptive anti-tumor immunity," said Dr. Hallam. "The results here support the clinical evaluation of STRO-002 in combination with anti-PD1 or anti-PD-L1 agents. While we believe STRO-002 as a single agent may demonstrate clinical benefit in certain tumors resistant to checkpoint inhibitor monotherapies, we are excited at the prospect of evaluating potential additional positive impacts on cancer patients that may result from combination treatment regimens involving STRO-002 with other checkpoint inhibitors."

"An important part of our STRO-002 clinical development strategy includes evaluating these data to determine an optimal combination regimen to take into clinical trials," said Sutro Chief Medical Officer, Arturo Molina, M.D. "We anticipate evaluating STRO-002 in combination studies in addition to our single agent studies. We currently expect to initiate a STRO-002 combination clinical trial in 2021."

STRO-002 is an antibody-drug conjugate directed against FolRα, a membrane receptor glycoprotein, which is highly expressed in ovarian cancer and endometrial cancer and is composed of a FolRα antibody conjugated to a tubulin inhibitor hemiasterlin using a cleavable linker.

A Phase 1, open-label, multicenter, dose escalation trial with dose expansion of STRO-002 is ongoing, designed to identify the maximum tolerated dose, the recommended Phase 2 clinical dose, and to evaluate the safety, tolerability, and preliminary anti-tumor activity of STRO-002 in adults with advanced epithelial ovarian cancer, including fallopian or primary peritoneal cancer, and endometrial cancer. The trial is registered with clinicaltrials.gov identifier NCT03748186. Sutro discovered, developed and manufactures STRO-002 using its proprietary XpressCF+ cell-free protein synthesis technology.

Presentation Details:

Title: STRO-002, an anti-FolRα ADC, demonstrates immune-modulating properties
and potentiates PD-L1 blockade
Abstract Number: 2250
Session Title: Immune Mechanisms Invoked by Therapies 2
Date/Time: June 22, 2020, 9:00 a.m. – 6:00 p.m. EDT
Presenter: Trevor Hallam, Ph.D.

The e-poster presentation can be found on the AACR (Free AACR Whitepaper) website and is also accessible through the Clinical/Scientific Presentation and Publication Highlights page of the News section of Sutro Biopharma’s website at www.sutrobio.com on the day of the poster presentation.

Additionally, on June 24th Sutro’s partner Merck KGaA, Darmstadt, Germany, will be presenting preclinical data from the collaboration’s pre-Development Candidate, M1231, a first-in-class bispecific antibody-drug conjugate targeting EGFR and MUC1.

Presentation Details:

Title: M1231: A first-in-class bispecific antibody-drug conjugate targeting EGFR
and MUC1
Abstract Number: 5686
Session Title: Emerging Mechanisms of Resistance to Targeted Therapies
Date/Time: June 24, 2020, 10:05 a.m. – 10:15 a.m. EDT
Presenter: Jan Anderl, Ph.D.

On June 19, 2020 Ultragenyx Pharmaceutical Inc. (NASDAQ: RARE), a biopharmaceutical company focused on the development and commercialization of novel products for rare and ultra-rare diseases, and Kyowa Kirin Co., Ltd. (Kyowa Kirin, TSE: 4151), a global specialty pharmaceutical company creating innovative medical solutions using the latest biotechnology, reported that the U.S. Food and Drug Administration (FDA) has approved Crysvita (burosumab) for the treatment of fibroblast growth factor 23 (FGF23)-related hypophosphatemia in tumor-induced osteomalacia (TIO) associated with phosphaturic mesenchymal tumors that cannot be curatively resected or localized in adults and pediatric patients 2 years of age and older (Press release, Kyowa Hakko Kirin, JUN 19, 2020, View Source [SID1234561221]). Crysvita is a human antibody that blocks excess activity of FGF23, a hormone that causes phosphate urinary excretion and suppresses active vitamin D production by the kidney.

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"For approximately half of all individuals with TIO, surgical removal of the tumors is not possible, leaving these patients with no other treatment options. The FDA approval of Crysvita marks the first treatment option that addresses the cause of the severe hypophosphatemia and osteomalacia resulting from these rare tumors," said Camille L. Bedrosian, M.D., Chief Medical Officer of Ultragenyx. "We plan to leverage our experience and existing infrastructure with Crysvita in X-linked hypophosphatemia to bring this important medicine to patients living with the rare, painful and debilitating disorder of TIO."

"Since its approval, Crysvita has meant a great deal to patients and families that previously had no other treatment options. We are proud of the work that has been done to advance this discovery from our labs, through a robust clinical research program, and through the FDA’s priority review process, to make this treatment available to patients with TIO," said Gary Zieziula, President, North America for Kyowa Kirin. "Our commitment to meeting the needs of patients with rare and serious diseases remains steadfast and we will continue to partner with the Ultragenyx team to address these needs with urgency."

TIO is a rare disease caused by typically benign, slow-growing tumors that produce excess levels of FGF23, which is involved in phosphate reabsorption. Patients with TIO can experience

symptoms including severe hypophosphatemia (low levels of phosphate in the blood), osteomalacia (softening of the bones), muscle weakness, fatigue, bone pain and fractures. There are an estimated 500 to 1,000 people in the United States with TIO, and approximately half of all cases are believed to be inoperable. In patients for whom the tumor or lesion is inoperable, the current treatment consists of oral phosphate and/or active vitamin D replacement. Efficacy of this management is often limited, and its benefits must be balanced with monitoring for potential risks.

This is the second FDA-approved indication for Crysvita, which was first approved in April 2018 for the treatment of X-linked hypophosphatemia (XLH) in adult and pediatric patients one year of age and older. The XLH indication was expanded in September 2019 to include infants as young as six months of age.

The FDA approval of Crysvita for TIO was based on data from two single-arm Phase 2 studies, a 144-week study in 14 adult patients conducted by Ultragenyx in the United States and an 88-week study in 13 adult patients conducted by Kyowa Kirin in Japan and South Korea. In both studies, Crysvita was associated with increases in serum phosphorus and serum 1,25-dihydroxyvitamin D levels. Increased phosphate levels led to improvements in osteomalacia. Additionally, whole body bone scans demonstrated reduced tracer uptake with long-term treatment suggesting healing of bone lesions. Most common adverse reactions (>10%) in TIO patients are: tooth abscess, muscle spasms, dizziness, constipation, injection site reaction, rash, and headache.

The FDA granted Priority Review designation for the supplemental BLA for TIO, which is reserved for drugs that treat a serious condition and, if approved, would provide a significant improvement in safety or effectiveness.

To support access, Ultragenyx has a program called UltraCare, which helps patients and caregivers understand insurance coverage and assists them in finding financial support for Ultragenyx medicines including Crysvita, and for the administration of them. Dedicated in-house UltraCare Guides are available Monday through Friday from 9 a.m. to 8 p.m. Eastern Time at 888-756-8657.

About Crysvita
Crysvita (burosumab-twza) is a recombinant fully human monoclonal IgG1 antibody, discovered by Kyowa Kirin, against the phosphaturic hormone FGF23. FGF23 is a hormone that reduces serum levels of phosphorus and active vitamin D by regulating phosphate excretion and active vitamin D production by the kidney. Phosphate wasting in TIO and other hypophosphatemic conditions, including XLH, is caused by excessive levels and activity of FGF23. Crysvita is designed to bind to and thereby inhibit the biological activity of FGF23. By blocking excess FGF23 in patients with TIO and XLH, Crysvita is intended to increase phosphate reabsorption from the kidney and increase the production of active vitamin D, which enhances intestinal absorption of phosphate and calcium.

Crysvita is approved by the U.S. FDA for the treatment of X-linked hypophosphatemia (XLH) in adult and pediatric patients six months of age and older and FGF23-related hypophosphatemia in

tumor-induced osteomalacia (TIO) associated with phosphaturic mesenchymal tumors that cannot be curatively resected or localized in adults and pediatric patients 2 years of age and older, and by Health Canada and Brazil’s National Health Surveillance Agency (ANVISA) for the treatment of XLH in adult and pediatric patients one year of age and older. In Japan, it is approved by the Ministry of Health, Labor and Welfare (MHLW) for the treatment of FGF23-related hypophosphatemic rickets and osteomalacia. In Europe, Crysvita has received European conditional marketing authorization for the treatment of XLH with radiographic evidence of bone disease in children 1 year of age and older and adolescents with growing skeletons, and an application for the expanded use in adults with XLH is currently under review by the European Medicines Agency.

Kyowa Kirin and Ultragenyx have been collaborating in the development and commercialization of Crysvita globally based on the collaboration and license agreement between the parties.

U.S. INDICATION

Crysvita (burosumab-twza) is a fibroblast growth factor 23 (FGF23)-blocking antibody indicated for the treatment of:

X-linked hypophosphatemia (XLH) in adult and pediatric patients 6 months of age and older.

FGF23-related hypophosphatemia in tumor-induced osteomalacia (TIO) associated with phosphaturic mesenchymal tumors that cannot be curatively resected or localized in adult and pediatric patients 2 years of age and older.

IMPORTANT SAFETY INFORMATION

CONTRAINDICATIONS

With oral phosphate and/or active vitamin D analogs (e.g., calcitriol, paricalcitol, doxercalciferol, calcifediol).

When serum phosphorus is within or above the normal range for age.

In patients with severe renal impairment or end stage renal disease.

WARNINGS AND PRECAUTIONS

Hypersensitivity

Discontinue Crysvita if serious hypersensitivity reactions occur and initiate appropriate medical treatment.

Hyperphosphatemia and Risk of Nephrocalcinosis

For patients already taking Crysvita, dose interruption and/or dose reduction may be required based on a patient’s serum phosphorus levels.

Patients with TIO who undergo treatment of the underlying tumor should have dosing interrupted and adjusted to prevent hyperphosphatemia.

Injection Site Reactions

Discontinue Crysvita if severe injection site reactions occur and administer appropriate medical treatment.

ADVERSE REACTIONS

Pediatric XLH Patients

Adverse reactions reported in 10% or more of Crysvita-treated pediatric XLH patients across all studies are: pyrexia, injection site reaction, cough, vomiting, pain in extremity, headache, tooth abscess, dental caries, diarrhea, vitamin D decreased, toothache, constipation, myalgia, rash, dizziness, and nausea.

Post-marketing experience reported in pediatric XLH patients receiving Crysvita – blood phosphorus increased.

Adult XLH Patients

Adverse reactions reported in more than 5% of Crysvita-treated adult XLH patients and in at least 2 patients more than placebo in one study are: back pain, headache, tooth infection, restless legs syndrome, vitamin D decreased, dizziness, constipation, muscle spasms, and blood phosphorus increased.

Spinal stenosis is prevalent in adults with XLH, and spinal cord compression has been reported. It is unknown if Crysvita therapy exacerbates spinal stenosis or spinal cord compression.

Adult TIO Patients

Adverse reactions reported in more than 10% of Crysvita-treated adult TIO patients in two studies are: tooth abscess, muscle spasms, dizziness, constipation, injection site reaction, rash, and headache.

USE IN SPECIFIC POPULATIONS

There are no available data on Crysvita use in pregnant women to inform a drug-associated risk of adverse developmental outcomes. Serum phosphorus levels should be monitored throughout pregnancy. Report pregnancies to the Kyowa Kirin, Inc. Adverse Event reporting line at
1-888-756-8657.

There is no information regarding the presence of Crysvita in human milk or the effects of Crysvita on milk production or the breastfed infant.

PATIENT COUNSELING INFORMATION

Advise patients not to use any oral phosphate and/or active vitamin D analog products.

Instruct patients to contact their physician if hypersensitivity reactions, injection site reactions, and restless leg syndrome induction or worsening of symptoms occur.

On June 19, 2020 AVEO Oncology (Nasdaq: AVEO) reported the closing of its previously announced underwritten public offering of 9,725,000 shares of its common stock, which includes the partial exercise by the underwriters of their option to purchase an additional 1,225,000 shares, at a price to the public of $5.25 per share (Press release, AVEO, JUN 19, 2020, View Source [SID1234561259]). The aggregate gross proceeds to AVEO from the offering were approximately $51.1 million, before deducting underwriting discounts and commissions and offering expenses payable by AVEO.

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The net proceeds of the offering are expected to be used for working capital and general corporate purposes, including funding commercialization activities relating to tivozanib.

SVB Leerink and Stifel acted as joint bookrunning managers for the offering. Baird and H.C. Wainwright & Co. acted as co-lead managers for the offering.

The shares were offered by AVEO pursuant to a shelf registration statement on Form S-3 that was filed with the Securities and Exchange Commission ("SEC") on November 30, 2017 and declared effective by the SEC on December 15, 2017.

A final prospectus supplement relating to, and describing the terms of, the offering has been filed with the SEC and is available on the SEC’s website at www.sec.gov.

Copies of the final prospectus supplement and the accompanying prospectus relating to this offering may also be obtained from SVB Leerink LLC, Attention: Syndicate Department, One Federal Street, 37th Floor, Boston, MA 02110, by telephone at (800) 808-7525, ext. 6218 or by email at [email protected]; or Stifel, Nicolaus & Company, Incorporated, Attention: Syndicate, One Montgomery Street, Suite 3700, San Francisco, CA 94104, by telephone at (415) 364-2720 or by email at [email protected].

This press release does not constitute an offer to sell or the solicitation of an offer to buy, nor shall there be any sale of these securities in any state or jurisdiction in which such offer, solicitation or sale would be unlawful prior to registration or qualification under the securities laws of any such state or jurisdiction.

On June 19, 2020 Roche (SIX: RO, ROG; OTCQX: RHHBY) reported that the phase III IPATential150 study met its co-primary endpoint of radiographic progression-free survival (rPFS) in patients with metastatic castration-resistant prostate cancer (mCRPC) and whose tumours had PTEN loss (Press release, Hoffmann-La Roche, JUN 19, 2020, View Source [SID1234561240]). In this patient group, ipatasertib in combination with abiraterone and prednisone/prednisolone provided a statistically significant reduction in the risk of disease worsening or death, compared to current standard of care (abiraterone and prednisone/prednisolone) plus placebo. The other co-primary endpoint of rPFS in the overall study population (ITT) was not met. The safety profile for the combination of ipatasertib and abiraterone was consistent with previous analyses and known risks. The results of the IPATential150 study will be presented at an upcoming medical meeting.

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While initial data are encouraging, overall survival benefit and additional secondary endpoints are not yet mature. The trial will continue until the next planned analysis and data will be shared with health authorities.

"Prostate cancer remains a leading cause of death in men worldwide and patients with metastatic castration-resistant prostate cancer can be difficult to treat," said Levi Garraway, M.D., Ph.D., Roche’s Chief Medical Officer and Head of Global Product Development. "The early results of the IPATential150 study are encouraging in our ongoing mission to develop new treatment options for people with advanced prostate cancer."

Ipatasertib is an oral, highly specific, investigational medicine designed to target and bind to all three isoforms of AKT (protein kinase B), which blocks the PI3K/AKT signalling pathway – a key driver of cancer cell growth and proliferation in prostate cancer.1,2 The PI3K/AKT pathway has also been implicated in resistance to anti-androgen therapy as androgen receptor (AR) inhibition is associated with an increase in AKT pathway activation.2,3 Functional loss of the tumour suppressor protein PTEN within the tumour, seen in approximately 40-60% of mCRPC patients, results in hyperactivation of the PI3K/AKT pathway and is associated with adverse outcomes such as increased tumour grade and stage, earlier biochemical recurrence after radical prostatectomy, metastasis, prostate-cancer-specific death, and androgen-independent progression.4,5

Roche’s clinical development programme for ipatasertib focuses on tumours that are frequently found to have activation of the PI3K/AKT pathway. In addition to prostate cancer, ipatasertib is being studied in certain types of breast cancer including triple-negative breast cancer (TNBC) and hormone-receptor positive (HR+), HER2- negative breast cancer. Results are anticipated later in 2020.

About the IPATential150 study6
IPATential150 is a double-blind, placebo-controlled, randomised phase III study assessing ipatasertib in combination with abiraterone and prednisone/prednisolone, compared to placebo plus abiraterone and prednisone/prednisolone, in adult male patients with asymptomatic or mildly symptomatic, previously untreated mCRPC.

The co-primary endpoints of the study are investigator-determined rPFS in the overall study population, as well as a subpopulation whose tumours have PTEN loss, as assessed by immunohistochemistry (Ventana assay). PFS in the study is defined as the time from date of randomisation to the first occurrence of disease progression or death from any cause, whichever occurs earlier. Secondary endpoints include overall survival, safety, time to pain progression, time to initiation of cytotoxic chemotherapy and time to function deterioration.

About ipatasertib
Ipatasertib is an oral, highly specific, investigational medicine designed to target and bind to all three isoforms of AKT, which blocks the PI3K/AKT signalling pathway and may prevent cancer cell growth and survival.1,2

Ipatasertib is being studied in tumours that are frequently found to have activation of the PI3K/AKT pathway, including breast and prostate cancers. Clinical studies are ongoing to evaluate the efficacy and safety of ipatasertib and the opportunity it may provide to address significant unmet needs for patients with these diseases.

Ipatasertib was discovered at Genentech in partnership with Array BioPharma Inc. (acquired by Pfizer Inc. on July 30, 2019).

About metastatic castration-resistant prostate cancer (mCRPC)
Prostate cancer is the second most frequent cancer and the fifth leading cause of death in men.7 Metastatic prostate cancer refers to prostate cancer that has spread beyond the prostate to other parts of the body (metastasised).8 Although most men are cured with treatment of localised disease, recurrent or newly diagnosed metastatic disease is associated with significant morbidity and mortality.9,10,11

Primary treatment of advanced prostate cancer is androgen deprivation therapy (ADT); however, up to one-third of patients will progress despite reduction in serum testosterone levels to castrate levels (<50 ng/dL), either through surgical or medical castration.12,13 Castration-resistant prostate cancer (CRPC) is defined by disease progression, as measured by prostate specific antigen (PSA) or radiographic measures, despite adequate suppression of serum testosterone levels.14,15 Despite the current availability of life-extending therapies for mCRPC, the majority of men will die of their disease: the median life expectancy in this population is less than three years.16,17

Prostate cancer growth and survival is driven by abnormal AR signalling. In CRPC, cell growth and proliferation is also commonly driven by activation of the PI3K/AKT signalling pathway.1,2 In particular, functional loss of the tumour suppressor protein PTEN within the tumour, seen in approximately 40-60% of people with mCRPC, results in hyperactivation of the PI3K/AKT pathway.4 PTEN loss is associated with adverse outcomes such as increased tumour grade and stage, earlier biochemical recurrence after radical prostatectomy, metastasis, prostate-cancer-specific death, and androgen-independent progression.5 The PI3K/AKT pathway has also been implicated in resistance to anti-androgen therapy as AR inhibition is associated with an increase in AKT pathway activation, suggesting that the tumour compensates for the loss of one pathway with another.2,3

About Roche in prostate cancer
For more than 50 years, Roche has been developing medicines with the goal of redefining treatment in oncology. Our research and development aim is to provide effective cancer therapies through the discovery and development of novel therapeutics that target the specific molecular pathways associated with cancer. Roche is expanding into additional areas of unmet need, working to find innovative solutions for diseases such as prostate cancer, the most prevalent cancer in men and fifth leading cause of cancer-related male death worldwide.5 Roche is committed to research into genitourinary cancers, including bladder and renal cancers, and to providing life extending treatment options for these patients.