On May 29, 2020 Agendia, Inc., a world leader in precision oncology for breast cancer, reported that new data from ongoing clinical research on MammaPrint and BluePrint was debuted at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) 2020 Virtual Scientific Program (ASCO) (Free ASCO Whitepaper) (Press release, Agendia, MAY 29, 2020, View Source [SID1234558767]). A total of five posters were presented on Agendia’s genomic profiling assays.

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The highlighted data below further illustrate the efficacy of Agendia’s MammaPrint and BluePrint genomic testing to consistently stratify breast cancers, allowing for a highly personalized regimen throughout a patient’s treatment journey. The latest findings from Agendia deliver immediate, actionable information for doctors and patients early in the diagnosis and treatment planning process and build on research that will impact breast cancer treatment and outcomes in the future.

One scientific presentation, entitled "Adding precision to 2018 ASCO (Free ASCO Whitepaper)/CAP HER2 testing guidelines in breast cancer with genomic profiling," evaluated the concordance between human epidermal growth factor receptor 2 (HER2) status as put forth by the 2018 ASCO (Free ASCO Whitepaper)/CAP guidelines and Agendia’s BluePrint genomic testing. In this real-world diagnostic data set, the 2018 guideline recommendations led to fewer HER2 equivocal tumors overall, confirming the positive impact of the revisions. Of note, BluePrint reclassified 69 percent of HER2-positive tumors and all HER2 equivocal tumors to non-HER2 molecular subtypes, indicating that these tumors may have suboptimal responses to HER2-directed therapy. This study found that molecular classification by BluePrint adds further precision in stratifying HER2-positive patients, offering the potential to predict responsiveness to HER2-targeted therapies.

"In this study, nearly 70 percent of HER2-positive diagnoses were reclassified to non-HER2, based on molecular subtyping. This is interesting and may have the potential at some point to affect treatment decisions and patient outcomes," said Adam Brufsky, MD, PhD, and Professor of Medicine at the University of Pittsburgh School of Medicine. "Data continue to show the value of MammaPrint and BluePrint as diagnostic tools that allow physicians to make more informed decisions to address their patients’ disease."

Also at ASCO (Free ASCO Whitepaper), Agendia shared updates on the ongoing FLEX trial, the massive real-world clinical data set designed to drive the medical community forward in its approach to precision medicine. In addition to a designated FLEX study poster – "The FLEX Real World Data Platform Explores New Gene Expression Profiles and Investigator-Initiated Protocols in Early Stage Breast Cancer" – that gave general updates on the registry, Agendia also highlighted FLEX and forward-looking studies, one of which has immediate implications for how a patient’s treatment may change based on comprehensive information uncovered by BluePrint.

The FLEX scientific presentation, entitled, "TNBC subtype and clinical estrogen receptor status of genomically basal breast tumors in Caucasian, African American, and Latin American patients," evaluated the distribution of triple-negative breast cancer (TNBC) subtypes in genomically Basal-Type cancers from self-reported patient ethnicities (Caucasian, African American, and Latin American). The data show that Basal-Type tumors are heterogeneous and include all defined TNBC subtypes, independent of ethnicity.

In addition, the study evaluated the association of IHC-determined estrogen receptor status and Basal-Type tumors of each ethnicity. Analyses demonstrated that BluePrint reclassified a subset of estrogen receptor positive (ER+) tumors to molecular Basal-Type and that ER status was not significantly associated with a specific TNBC subtype or ethnicity. This highlights the clinical need to trace basal biology in ER+ patients to refine treatment for basal-like tumors.

"The reclassification of a subset of ER+ tumors identifies an urgent and actionable situation," said Cathy Graham, MD, Assistant Professor of Surgery in the Division of Surgical Oncology at Emory University School of Medicine and Director, Breast Surgery at Emory St. Joseph’s Hospital. "From a clinical perspective, when these patients are first diagnosed, they appear to have luminal breast cancer. But, when you are able to look at the underlying mechanism with comprehensive genomic testing, a large subset of these breast cancers is reclassified to Basal-Type, which is high risk. This knowledge allows us to execute a more personalized and precise treatment approach immediately."

Two other forward-looking studies reinforce the future utility of better stratifying patients, and Agendia’s ability to provide a more sophisticated platform for discovery in gene signature research.

In the first, entitled, "High Risk breast cancer genes at 8q22-24 and their role in over 5,000 patients evaluated with the MammaPrint risk of recurrence assay," FLEX researchers looked at the 8q22-24 chromosomal region, known to be associated with breast cancer. The study results provided further evidence that aberrations in this region are associated with higher-risk disease. Within the MammaPrint signature, the genes CCNE2, MTDH, and TSPYL5 have similar expression patterns and when overexpressed, represent a unique subgroup of high-risk tumors. These findings and further research on the 8q22-24 region may help to better stratify high-risk patients through ongoing clinical trials evaluating response and resistance to targeted therapies.
The second, entitled, "12-chemokine gene expression score in breast cancer patients treated with neoadjuvant chemotherapy," builds on existing research related to gene expression as a predictive biomarker for immune responses in breast cancer patients. The study found that chemokine gene expression, which indicates the presence of immune cells, was associated with pathologic complete response (pCR), MammaPrint High Risk index, and BluePrint subtypes. This research suggests that chemokine score may be further stratified by using MammaPrint and BluePrint in order to identify patients who may be more likely to benefit from neoadjuvant chemotherapy. This work also suggests that future studies may evaluate the potential utility for chemokine score and MammaPrint in predicting responses to immunotherapy in breast cancer patients.
"The research we are showcasing at this year’s ASCO (Free ASCO Whitepaper) Annual Meeting underscores our commitment to patients and physicians," said William Audeh, MD, Chief Medical Officer at Agendia. "With our growing arsenal of data collected through prospective clinical trials such as FLEX, I-SPY2 and MINDACT, we are able to help patients now while information-gathering for future breast cancer treatment strategy."

Agendia is proud to present these findings at the ASCO (Free ASCO Whitepaper) 2020 Annual Meeting, which underscore the company’s commitment to innovation and discovery through extraordinary, patient-focused research.

On May 29, 2020 Amgen (NASDAQ:AMGN) reported new data from the CodeBreaK 100 clinical development program evaluating investigational AMG 510 (proposed INN sotorasib) in heavily pretreated patients with a range of KRAS G12C-mutant solid tumors (Press release, Amgen, MAY 29, 2020, View Source [SID1234558766]). Updated Phase 1 data from patients with advanced colorectal cancer (CRC) and other selected solid tumors continued to demonstrate disease control activity, safety and tolerability. These data are being presented during the ASCO (Free ASCO Whitepaper)20 Virtual Scientific Program, May 29 – 31, 2020.

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"Targeting KRAS has been a 40-year quest leaving patients with limited treatment options. In just under two years in the clinic, we have seen encouraging early efficacy and safety data across a number of solid tumors," said David M. Reese, M.D., executive vice president of Research and Development at Amgen. "New Phase 1 data at ASCO (Free ASCO Whitepaper) show that, in some patients with advanced colorectal cancer, sotorasib monotherapy provided prolonged disease control. A Phase 2 monotherapy study in advanced colorectal cancer has fully enrolled and will provide further insights into the potential utility of sotorasib in this disease."

Sotorasib Activity in Patients With Advanced Colorectal Cancer
CRC is the second leading cause of cancer deaths worldwide.1 It is the third most commonly diagnosed cancer globally and incidence is expected to grow by more than 20% over the next decade.2 For patients with previously treated metastatic CRC receiving standard therapies, unmet need remains high, with median progression-free survival (PFS) of about 2 months and response rates of less than 2%.3,4

This Phase 1 dose escalation study evaluated 42 heavily pretreated patients with advanced KRAS G12C-mutant CRC (data cut-off of Jan. 2020). All patients received prior systemic therapies (median of three prior lines), with 69% having received three or more prior lines of therapy. Twenty-two (52.4%) and eight (19.0%) patients remained on treatment for more than three and six months, respectively.

In the 960 mg once-daily target dose cohort, the objective response rate (ORR) was 12% (3/25) and the disease control rate (DCR) was 80% (20/25). Median PFS was 4.2 months and overall survival (OS) had not been reached after a median follow-up of almost 8 months. Tumor shrinkage was observed in 11 of 23 patients with available post-baseline tumor data.

Across all dose levels, the majority of patients achieved disease control, with an ORR of 7.1% and a DCR of 76.2%. Disease stability was maintained for a median of 4.2 months. Median PFS was 4.0 months and median OS was 10.1 months. Tumor shrinkage was observed in 18 of 39 patients with available post-baseline tumor data across all doses.

"There is currently a tremendous treatment gap for patients with advanced KRAS G12C-mutant colorectal cancer," said Marwan G. Fakih, M.D., primary study investigator and co-director of the Gastrointestinal Cancer Program, City of Hope, Duarte, California. "These latest sotorasib data continue to show encouraging antitumor activity and tolerability in a patient population that has few treatment options."

Disease progression was the most common reason for treatment discontinuation. The majority of treatment-related adverse events (TRAEs) were Grade 1 and 2. Only two TRAEs were Grade 3 (diarrhea and anemia). There were no Grade 4 or higher TRAEs.

Sotorasib Activity in Patients With Advanced Solid Tumors Other Than NSCLC or CRC
Data were evaluated for 25 heavily pretreated patients with advanced KRAS G12C-mutant solid tumors other than CRC or NSCLC. These patients had received a median three prior lines of therapy with a median follow-up of 4.3 months.

These data demonstrated early evidence of a consistent safety profile and anticancer activity across a range of advanced KRAS G12C-mutant solid tumors, including pancreatic, appendiceal and endometrial cancer. Partial responses were confirmed in three patients with appendiceal, melanoma and endometrial cancer, respectively. Six of eight evaluable patients with pancreatic cancer achieved stable disease, and three had approximately a 30% reduction in tumor burden from baseline. Tumor shrinkage was observed in 13 of 19 evaluable patients with available post-baseline tumor data across all tumor types.

A complete listing of Amgen posters is available on the ASCO (Free ASCO Whitepaper) website at www.asco.org.

About KRAS
The subject of almost four decades of research, the RAS gene family contains the most frequently mutated oncogenes in human cancers.5,6 Within this family, KRAS is the most prevalent variant and is particularly common in solid tumors.5 A specific mutation known as KRAS G12C is found in approximately 13% of non-small cell lung cancers, 3% to 5% of colorectal cancers and 1% to 2% of numerous other solid tumors.7-9 The KRASG12C protein has been considered "undruggable" due to a lack of traditional small molecule binding pockets on the protein. Amgen is exploring the potential of KRASG12C inhibition across a broad variety of solid tumor types.

About CodeBreaK
The CodeBreaK clinical trial program for Amgen’s investigational drug sotorasib is designed to treat patients with multiple KRAS G12C-mutant solid tumors and address the longstanding unmet medical need for these cancers.

CodeBreaK 100, the Phase 1 and 2, first-in-human, open-label multicenter study, enrolled patients with KRAS G12C-mutant solid tumors. Eligible patients were heavily pretreated with at least two or more prior lines of treatment, consistent with their tumor type and stage of disease. The primary endpoint for the Phase 1 study is safety, and key secondary endpoints include objective response rate (assessed every six weeks), duration of response and progression-free survival. Patients were enrolled in four dose cohorts: 180 mg, 360 mg, 720 mg and 960 mg, taken orally once a day.

Amgen’s single-arm Phase 2 trials in both non-small cell lung cancer (NSCLC) and colorectal cancer (CRC) (also part of CodeBreaK 100) are now fully enrolled. The potentially registrational Phase 2 trial in NSCLC is on track for data readout in 2020. The Phase 2 CRC trial is expected to have a data readout in early 2021.

Amgen is currently enrolling six Phase 1b combination studies across various advanced solid tumors (CodeBreaK 101). In addition, a randomized global Phase 3 confirmatory study in NSCLC (CodeBreaK 200) has been initiated. Additional information about CodeBreaK clinical trials can be found at View Source

On May 29, 2020 Regeneron Pharmaceuticals, Inc. (NASDAQ: REGN) and Sanofi reported new, longer-term data for PD-1 inhibitor Libtayo (cemiplimab-rwlc) from a pivotal Phase 2 trial in advanced cutaneous squamous cell carcinoma (CSCC), the deadliest non-melanoma skin cancer (Press release, Regeneron, MAY 29, 2020, View Source [SID1234558765]). These results demonstrate both longer durability and higher complete response (CR) rates than previously reported. Furthermore, the data make up part of the largest and most mature prospective clinical dataset in patients with metastatic CSCC (mCSCC) or locally advanced CSCC (laCSCC) who are not candidates for curative surgery or radiation. The data were presented during the virtual 2020 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting.

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"The three-year follow-up data demonstrate significant long-term outcomes with Libtayo, which is now standard-of-care for patients with advanced CSCC in many countries," said Dr. Danny Rischin, Director, Department of Medical Oncology at Peter MacCallum Cancer Centre, Victoria, Australia. "The Libtayo data on duration of response and overall survival provide new insights into the longer-term treatment of advanced CSCC, with the median still not reached for either measure. Remarkably, it is exciting to see the number of complete responses increase with longer follow-up, which reinforces the potential ongoing benefit of Libtayo treatment in this aggressive skin cancer."

With up to three years of follow-up, results from the pivotal Phase 2 trial showed 46% of patients (95% CI: 39%-53%) experienced substantial tumor shrinkage following Libtayo treatment, with a median time to response of 2 months (interquartile range: 2-4 months). Furthermore, more patients (16%) saw their tumors disappear completely over time compared to previous analyses. Among patients with metastatic disease who had the longest available follow-up (Group 1 in table below), 20% of patients have now achieved a CR, increasing from 7% in the 2017 primary analysis. Among patients who achieved a CR in any group, median time to CR was 11 months (interquartile range: 7-15 months). Median overall survival and median duration of response have yet to be reached for any treatment group.

Results by treatment group were as follows:

Group 1:

mCSCC

3 mg/kg every

2 weeks

(n=59)

Group 2:

laCSCC

3 mg/kg every
2 weeks

(n=78)

Group 3:

mCSCC

350 mg every

3 weeks

(n=56)

Total

(n=193)

Median duration of follow-up (range)

19 months

(1–36)

16 months

(1–36)

17 months

(1–26)

16 months

(1–36)

Objective response rate (95% confidence interval [CI])

51%

(38%–64%)

45%

(34%–57%)

43%

(30%–57%)

46%

(39%–53%)

CR (n)

20%

(12)

13%

(10)

16%

(9)

16%

(31)

Partial response (n)

31%

(18)

32%

(25)

27%

(15)

30%

(58)

Median observed time to response (interquartile range)*

2 months

(2–2)

2 months

(2–4)

2 months

(2–4)

2 months

(2–4)

Median observed time to CR (interquartile range)

11 months

(7–18)

10 months

(7–13)

12 months

(8–17)

11 months

(7–15)

Median duration of response (95% CI)*

Not reached

(21, NE)

Not reached

(18, NE)

Not reached

(NE, NE)

Not reached

(29, NE)

Median overall survival

Not reached

Not reached

Not reached

Not reached

NE = not evaluable

*Based on number of patients with confirmed complete or partial response and Kaplan-Meier estimation.

CR rates over time were as follows:

Group 1:

mCSCC

3 mg/kg every

2 weeks

Group 2:**

laCSCC

3 mg/kg every
2 weeks

Group 3:

mCSCC

350 mg every

3 weeks

Primary analysis, CR % (n)

7%

(4)

13%

(10)

5%

(3)

Approximately 1 year of follow-up, CR % (n)

17%

(10)

13%

(10)

16%

(9)

Approximately 2 years of follow-up, CR % (n)

20%

(12)

NE

NE

**Among 23 laCSCC patients who were included in the pre-specified Group 2 interim analysis, there were no CRs.

No new safety signals were identified. The most common treatment-emergent adverse events (AEs) were fatigue (35%), diarrhea (28%) and nausea (24%). The most common grade 3 or higher treatment-related AEs were pneumonitis (3%), autoimmune hepatitis (2%), anemia, colitis and diarrhea (each 1%). No new AEs resulting in death were reported compared to previous reports.

In addition to the updated efficacy and safety data, a separate post-hoc analysis of health-related quality of life (HRQL) outcomes from the Phase 2 trial was presented for the first time. A significant majority (91%) of patients reported improved or stable overall HRQL and 43% of patients experienced a clinically meaningful reduction in pain by the end of the assessment period. The analysis was based on patient responses to the European Platform of Cancer Research cancer specific 30-item HRQL questionnaire (QLQ-C30).

The open-label, single-arm, global, pivotal Phase 2 trial (Study 1540) enrolled 193 patients with laCSCC or mCSCC who were not candidates for curative surgery or radiation. The initial primary analysis of the trial, along with results from a Phase 1 trial (Study 1423), supported the U.S. Food and Drug Administration (FDA) approval of Libtayo in late 2018. Together, the trials represent the largest and most mature prospective clinical dataset in advanced CSCC.

Libtayo is being jointly developed by Regeneron and Sanofi under a global collaboration agreement. Libtayo was invented using Regeneron’s proprietary VelocImmune technology that utilizes a proprietary genetically-engineered mouse platform endowed with a genetically-humanized immune system to produce optimized fully-human antibodies. VelocImmune technology has been used to create multiple antibodies including Dupixent (dupilumab), Praluent (alirocumab) and Kevzara (sarilumab), which are approved in multiple countries around the world. Regeneron previously used these technologies to rapidly develop a treatment for Ebola virus infection, which is currently under review by the FDA, and is now being used in efforts to create preventative and therapeutic medicines for COVID-19.

About CSCC
CSCC is the second most common type of skin cancer in the world, accounting for approximately 20% of all skin cancers, and the number of newly diagnosed cases is expected to rise substantially in many countries. Although CSCC has a good prognosis when caught early, the cancer can prove especially difficult to treat effectively when it is advanced, and patients can experience reduced quality of life due to the impact of the disease as it progresses. While estimates vary, sources suggest that 7,000 patients in the U.S. die annually of advanced CSCC, which is comparable to the number of deaths caused by melanoma.

About Libtayo
Libtayo is a fully-human monoclonal antibody targeting the immune checkpoint receptor PD-1 on T-cells. By binding to PD-1, Libtayo has been shown to block cancer cells from using the PD-1 pathway to suppress T-cell activation.

Libtayo is the first and only immunotherapy approved in the U.S., EU, and other countries for adults with mCSCC or laCSCC who are not candidates for curative surgery or curative radiation. In the U.S., the generic name for Libtayo in its approved indication is cemiplimab-rwlc, with rwlc as the suffix designated in accordance with Nonproprietary Naming of Biological Products Guidance for Industry issued by the U.S. Food and Drug Administration.

The extensive clinical program for Libtayo is focused on difficult-to-treat cancers. In skin cancer, this includes a pivotal trial in advanced basal cell carcinoma and additional trials in adjuvant and neoadjuvant CSCC. Libtayo is also being investigated in pivotal Phase 3 trials in non-small cell lung cancer and cervical cancer, as well as in trials combining Libtayo with novel therapeutic approaches for both solid tumors and blood cancers. These potential uses are investigational, and their safety and efficacy have not been evaluated by any regulatory authority.

IMPORTANT SAFETY INFORMATION AND INDICATION FOR U.S. PATIENTS

What is the most important information I should know about Libtayo?
Libtayo is a medicine that may treat a type of skin cancer by working with your immune system. Libtayo can cause your immune system to attack normal organs and tissues in any area of your body and can affect the way they work. These problems can sometimes become severe or life-threatening and can lead to death. These problems may happen anytime during treatment or even after your treatment has ended.

Call or see your healthcare provider right away if you develop any symptoms of the following problems or these symptoms get worse:

Lung problems (pneumonitis). Signs and symptoms of pneumonitis may include new or worsening cough, shortness of breath, and chest pain.
Intestinal problems (colitis) that can lead to tears or holes in your intestine. Signs and symptoms of colitis may include diarrhea (loose stools) or more frequent bowel movements than usual; stools that are black, tarry, sticky or that have blood or mucus; and severe stomach-area (abdomen) pain or tenderness.
Liver problems (hepatitis). Signs and symptoms of hepatitis may include yellowing of your skin or the whites of your eyes, severe nausea or vomiting, pain on the right side of your stomach area (abdomen), drowsiness, dark urine (tea colored), bleeding or bruising more easily than normal, and feeling less hungry than usual.
Hormone gland problems (especially the adrenal glands, pituitary, thyroid and pancreas). Signs and symptoms that your hormone glands are not working properly may include headaches that will not go away or unusual headaches, rapid heartbeat, increased sweating, extreme tiredness, weight gain or weight loss, dizziness or fainting, feeling more hungry or thirsty than usual, hair loss, feeling cold, constipation, deeper voice, very low blood pressure, urinating more often than usual, nausea or vomiting, stomach-area (abdomen) pain, and changes in mood or behavior, such as decreased sex drive, irritability, or forgetfulness.
Kidney problems, including nephritis and kidney failure. Signs of these problems may include decrease in your amount of urine, blood in your urine, swelling in your ankles, and loss of appetite.
Skin problems. Signs of these problems may include rash, itching, skin blistering, and painful sores or ulcers in the mouth, nose, throat, or genital area.
Problems in other organs. Signs of these problems may include headache, tiredness or weakness, sleepiness, changes in heartbeat (such as beating fast, seeming to skip a beat, or a pounding sensation), confusion, fever, muscle weakness, balance problems, nausea, vomiting, stiff neck, memory problems, seizures (encephalitis), swollen lymph nodes, rash or tender lumps on skin, cough, shortness of breath, vision changes, or eye pain (sarcoidosis), seeing or hearing things that are not there (hallucinations), severe muscle weakness, low red blood cells (anemia), bruises on the skin or bleeding, and changes in eyesight.
Rejection of a transplanted organ. Your doctor should tell you what signs and symptoms you should report and monitor you, depending on the type of organ transplant that you have had.
Infusion (IV) reactions that can sometimes be severe and life-threatening. Signs of these problems may include chills or shaking, itching or rash, flushing, shortness of breath or wheezing, dizziness, fever, feeling of passing out, back or neck pain, and facial swelling.
Getting medical treatment right away may help keep these problems from becoming more serious.

Your healthcare provider will check you for these problems during your treatment with Libtayo. Your healthcare provider may treat you with corticosteroid or hormone replacement medicines. Your healthcare provider may delay or completely stop treatment if you have severe side effects.

Before you receive Libtayo, tell your healthcare provider about all your medical conditions, including if you:

have immune system problems such as Crohn’s disease, ulcerative colitis, or lupus;
have had an organ transplant;
have lung or breathing problems;
have liver or kidney problems;
have diabetes;
are pregnant or plan to become pregnant; Libtayo can harm your unborn baby.
Females who are able to become pregnant:
Your healthcare provider will give you a pregnancy test before you start treatment.
You should use an effective method of birth control during your treatment and for at least 4 months after your last dose of Libtayo. Talk with your healthcare provider about birth control methods that you can use during this time.
Tell your healthcare provider right away if you become pregnant or think you may be pregnant during treatment with Libtayo.
are breastfeeding or plan to breastfeed. It is not known if Libtayo passes into your breast milk. Do not breastfeed during treatment and for at least 4 months after the last dose of Libtayo.
Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements.

The most common side effects of Libtayo include tiredness, rash, and diarrhea. These are not all the possible side effects of Libtayo. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088. You may also report side effects to Regeneron Pharmaceuticals and Sanofi at 1-877-542-8296.

For more information, please see full Prescribing Information, including Medication Guide.

What is Libtayo?
Libtayo is a prescription medicine used to treat people with a type of skin cancer called cutaneous squamous cell carcinoma (CSCC) that has spread or cannot be cured by surgery or radiation.

It is not known if Libtayo is safe and effective in children.

On May 29, 2020 Medicenna Therapeutics Corp. ("Medicenna" or "the Company") (TSX: MDNA,OTCQB: MDNAF), a clinical stage immuno-oncology company, reported virtual presentations of data from its completed Phase 2b trial of MDNA55, an IL4-guided toxin, in patients with recurrent Glioblastoma (rGBM), at the 2020 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting (Press release, Medicenna Therapeutics, MAY 29, 2020, View Source [SID1234558764]).

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The oral poster discussion led by Dr. Ian F. Parney, MD, PhD (Mayo Clinic) and a presentation by Dr. John Sampson, MD, PhD (Robert H. and Gloria Wilkins Distinguished Professor of Surgery, Duke University School of Medicine), focused on additional data demonstrating clinical superiority of MDNA55 in patients with rGBM. The study enrolled rGBM patients that had aggressive tumors (de novo GBM, IDH wild-type, not-resectable at recurrence) with limited treatment options and poor survival outcomes [median overall survival ("mOS") of 6-9 months, median progression free survival ("mPFS") of < 2months and progression free survival ("PFS") at twelve months ("PFS-12") of 0%].

"Currently there are no approved therapies for rGBM that can extend survival by 50%, let alone by 70 – 100% as seen with MDNA55 after just one treatment," said Dr. John Sampson. "The data presented here reinforces our conviction that MDNA55 is an important player in glioblastoma and is a promising treatment option for this devastating disease."

"We’ve long believed that MDNA55 has the potential to present as a superior treatment option for improved survival and tumor control in patients with recurrent glioblastoma," says Dr. Fahar Merchant, President and Chief Executive Officer, Medicenna Therapeutics. "Further refinement of new and previously reported data using a rigorous propensity-matching methodology to remove any potential selection bias further bolsters this belief. For a treatment area that has seen limited innovation for more than 20 years, the MDNA55 phase 2 clinical trial data demonstrates strong evidence that MDNA55 could change the treatment paradigm for rGBM." The Company plans to submit an end of Phase 2 meeting package for MDNA55 to the FDA in Q2 2020.

Highlights from the ASCO (Free ASCO Whitepaper) presentation included:

Comparison of MDNA55 with an eligibility-matched Synthetic Control Arm ("SCA") demonstrated an improvement in mOS of 61%. When stratified by IL4R status, IL4R High subjects in the MDNA55 arm demonstrated improved mOS by 155% (Table 1).
Table 1.

Eligibility-Matched

Groups

N

mOS

Improvement

in mOS

Hazard

Ratio (HR)

OS-12

MDNA55 All-comers

44

12.4

61%

0.58

53%

SCA All-comers

81

7.7

25%

MDNA55 IL4R High

21

15.8

155%

0.54

62%

SCA IL4R High

17

6.2

24%

Further refinement of the SCA using propensity-score weighting (Li et al), an unbiased approach to select patients that match the baseline characteristics of MDNA55 treated patients based on 11 key baseline prognostic factors, confirms these results (Table 2).
Table 2.

Propensity-Weighted

Groups

N

mOS

Improvement

in mOS

HR

MDNA55 All-comers

43

12.4

72%

0.63

SCA All-comers

40.8

7.2

MDNA55 IL4R High

17

13.2

116%

0.52

SCA IL4R High

16.8

6.1

Irrespective of IL4R expression, subjects showed tumor control rate ("TCR") (tumor shrinkage or stabilization) of 76% based on modified RANO criteria; these subjects demonstrated mPFS of 4.6 months, PFS at six months ("PFS-6") of 40%, PFS-12 of 33%, mOS of 15.0 months and overall survival at twelve months ("OS-12") of 57%.
Additional updated results (not presented at ASCO (Free ASCO Whitepaper)) include the following:

Patients with Low IL4R expression (H-Score ≤ 60) had a similar TCR as patients with High IL4R expression (H-Score > 60); TCR of 75% vs. 76%, respectively. However, the majority of the IL4R Low patients (11 of 16) received high doses of MDNA55 (180 – 240 mg; median 180 mg) whereas only 8 of 21 IL4R High patients received the high dose of MDNA55.

The IL4R Low group receiving high dose also showed improved survival (mOS Not Reached, OS-12 of 53%) when compared to the low dose group (mOS = 8 months, OS-12 = 13%).

The Proposed Population (n=32), comprised of all IL4R High (irrespective of dose) as well as IL4R Low patients receiving the high dose, were shown to benefit the most from a single treatment of MDNA55. Median survival and OS-12 in this population was 15.8 months and 62% vs 7.0 months and 18%, respectively, when compared to the eligibility matched SCA. (Table 3).
Table 3.

TCR in the Proposed Population was 81% based on radiologic assessment by mRANO criteria.

These data indicate that MDNA55 has the potential to benefit all rGBM patients treated at the high dose (180 mg) irrespective of IL4R expression. The high dose has already shown an acceptable safety profile in this and earlier clinical trials (MTD = 240 mg).
The presentation and poster is available for on-demand viewing online at:
View Source

Reference:

Li F, Zaslavsky AM, Landrum MB. Propensity score weighting with multilevel data. Stat Med. 2013 Aug 30;32(19):3373-87.

On May 29, 2020 Medicenna Therapeutics Corp. ("Medicenna" or "the Company") (TSX: MDNA,OTCQB: MDNAF), a clinical stage immuno-oncology company, reported virtual presentation of data on MDNA11, one of its lead candidates from the IL-2 Superkine program, at the 2020 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting (Press release, Medicenna Therapeutics, MAY 29, 2020, View Source [SID1234558763]).

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The poster presentation by Dr. Moutih Rafei, PhD, (Associate Professor of Pharmacology and Physiology at the University de Montreal) focuses on new data arising from MDNA11, Medicenna’s novel long-acting interleukin-2 (IL-2) Superkine program.

"Recent transactions in the immuno-oncology and IL-2 space are evidence of the industry demand for drug candidates that can effectively boost the immune system of patients undergoing cancer treatment. The data we are sharing at ASCO (Free ASCO Whitepaper) show that MDNA11 has the potential to be a best-in-class IL-2 asset," says Dr. Fahar Merchant, Chief Executive Officer, Medicenna. "We are impressed by MDNA11’s preclinical profile, including its selectivity for immune effector cells, pharmacokinetics, safety and preclinical efficacy. We look forward to progressing MDNA11 towards the clinic in the next 12 months and to share these data with the ASCO (Free ASCO Whitepaper) community."

The poster presentation focuses on encouraging data in NHP for MDNA11, a long-acting IL-2 variant engineered to have enhanced affinity to CD122 without interacting with CD25. This allows MDNA11 to specifically expand cancer fighting naïve CD8 T cells as well as natural killer (NK) cells with minimal stimulation of T regulatory cells (Tregs) and eosinophils (associated with vascular leak syndrome). As such, the use of MDNA11 circumvents both immune-suppression and toxicity normally observed with standard IL-2 (Proleukin). In addition, MDNA11 has several advantages over other long-acting IL-2 variants as it permits enhanced accumulation in the tumor vicinity and can be recycled in vivo thus exhibiting prolonged circulation in the blood stream thereby reducing the frequency of treatment.

Highlights from the presentation include:

Half-life of MDNA11 (~7 hours) in mice is more than 20-fold longer than native IL-2 (~0.3 hr). The half-life of MDNA11 is 13-25 hours in NHP, comparable if not longer than other long-acting IL-2 molecules in development. Due to its durable pharmacodynamic (PD) effects that last up to 10 days, it circumvents the need for frequent dosing to achieve therapeutic efficacy.

In a pre-clinical tumor re-challenge study in a CT-26 mouse colon cancer model, two doses of MDNA11 over 2 weeks resulted in durable and complete responses in 60% of the mice when treated alone and 100% complete response when combined with an anti-CTLA4 antibody. These responses were durable, lasting over 210 days (7 months) despite multiple re-challenges with no additional treatment demonstrating sustained vaccine-like resistance. These results suggest that MDNA11 provides a complementary mechanism of immune activation when used alone or in combination with immune checkpoint inhibitors.

Kinetic studies in NHP showed a dose-dependent upregulation of Ki67 in CD8 T-cells lasting for almost two weeks post-MDNA11 administration, significantly longer than pegylated IL-2, and indicative of a prolonged PD effect.

When administered to NHP, MDNA11 demonstrated a dose dependent increase in absolute number of circulating CD8 T-cells, non-Treg CD4 T-cells and NK cells with minimal effect on Treg).

In spite of inducing a durable immune response, MDNA11 does not trigger cytokine storm nor cause other undesirable immune related side effects. These pre-clinical safety studies showed that MDNA11 did not lead to hypotension or vascular leak syndrome.

Additional safety features of MDNA11 include lack of immunogenicity (no anti-drug-antibody response), no change in liver and kidney function and no pulmonary edema as confirmed by histopathology.