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Replimune Presents Late-Breaking Abstract Featuring Data from IGNYTE Clinical Trial of RP1 Combined with Nivolumab in Anti-PD1 Failed Melanoma at the 39th Annual Meeting of the Society for Immunothera

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Oral presentation highlighting IGNYTE primary analysis data shows anti-tumor activity across all subgroups with injected and non-injected lesions responding with similar frequency, depth, duration, and kinetics

Initial biomarker data shows increase in tumor CD8+ T cell and PD-L1 expression after dosing along with an increase in gene signatures associated with CD8+ T cells and inflammatory cytokines, highlighting the potential of RP1 plus nivolumab to generate a potent anti-tumor immune response

WOBURN, Mass., Nov. 09, 2024 (GLOBE NEWSWIRE) — Replimune Group, Inc. (NASDAQ: REPL), a clinical stage biotechnology company pioneering the development of novel oncolytic immunotherapies, today announced that the primary analysis data from the IGNYTE clinical trial, including initial biomarker analyses, was presented as a late-breaking abstract during an oral session at the 39th Annual Meeting of the Society for Immunotherapy of Cancer (SITC 2024) in Houston, Texas. In addition, data from the ARTACUS clinical trial evaluating RP1 monotherapy in solid organ transplant patients with advanced cutaneous malignancies was also shared in an encore poster presentation during the meeting.

The initial biomarker analyses included in the SITC presentation which demonstrate increases in tumor CD8+ T cell infiltration and PD-L1 expression along with the induction of an immune inflammatory gene signature after treatment, further support the intended mechanism of RP1 in combination with nivolumab, including its ability to induce a systemic response after progression on prior anti-PD1 therapy, said Kostas Xynos, MD, PhD, MBA, Chief Medical (TASE:) Officer of Replimune. We believe that the systemic activity of RP1 and nivolumab is in particular demonstrated by the similar level of responses seen in both injected and non-injected lesions, including hard to treat visceral lesions, and by the durability of the responses seen.

IGNYTE Clinical Trial Data at SITC
The IGNYTE clinical trial cohort in anti-PD-1 failed melanoma included 140 patients who received RP1 plus nivolumab after confirmed progression while being treated for at least 8 weeks with anti-PD-1 based therapy, with or without anti-CTLA-4. The primary analysis by blinded independent central review was triggered once all patients had been followed for at least 12 months. The median follow-up at the time of the primary analysis was 15.4 months (0.5-47.6 months).

Data from the IGNYTE trial presented at SITC 2024 show:

  • One-third of patients experienced a confirmed response, with an overall response rate (ORR) of 33.6% by modified RECIST (mRECIST) v1.1 criteria, the primary endpoint in the trial protocol, and 32.9% by RECIST v1.1 criteria, an additional analysis requested by the FDA. The complete response (CR) rate by mRECIST v1.1 was 15%. In patients who had prior anti-PD1 and anti-CTLA-4, the ORR was 27.7% and for those who had primary resistance to anti-PD1, the ORR was 35.9% by mRECIST v1.1.
  • The median duration of response from response initiation was 21.6 months.
  • Most injected and non-injected lesions (85%) in responders had a 30% or greater reduction in size. RP1 plus nivolumab induced deep responses in non-injected lesions in visceral organs, including those distant from the injection site.
  • Median overall survival for the trial has not been reached, however, one-, two-, and three-year survival rates were 75.3%, 63.3%, and 54.8%, respectively. 12-month progression free survival (PFS) was 32.8% and median PFS was 3.7 months.

Initial biomarker data included in the SITC presentation show:

  • Tumor inflammation signature (TIS) and nano string analysis revealed an increase in the expression of genes associated with CD8+ T cells and inflammatory cytokines. These markers highlight the potential of RP1 plus nivolumab to generate a potent anti-tumor immune response. TIS is an investigational use only assay consisting of 18 genes that assesses the presence of an adaptive immune response, and which is associated with responsiveness to anti-PD1 therapy1.
  • Immunohistochemistry (IHC) images demonstrate that RP1 plus nivolumab may stimulate tumors to a more immune inflamed state, further highlighting the potential of RP1 plus nivolumab to reverse mechanisms of resistance to anti-PD1 therapy.

As previously reported, RP1  combined with nivolumab continues to be well-tolerated. Treatment-related adverse events associated with  RP1  in combination with nivolumab were predominantly Grade 1-2 constitutional type events (> 5% of patients), including fatigue, chills, pyrexia, nausea, influenza-like illness, injection-site pain, diarrhea, vomiting, headache, pruritis, asthenia, arthralgia, myalgia, decreased appetite, and rash, with a low incidence (12.8% of patients) of Grade 3-4 events, which were predominantly Grade 3. Grade 4 events were one each of lipase increased, cytokine release syndrome, myocarditis, hepatic cytolysis, and splenic rupture. There were no Grade 5 events.

The presentation is available on the Company website under  Events and Presentations.

The IGNYTE-3 confirmatory phase 3 trial evaluating RP1 plus nivolumab versus physician’s choice in patients with advanced melanoma who have progressed on anti-PD1 and anti-CTLA-4 or who are not candidates for anti-CTLA-4 therapy is currently recruiting. For additional information, visit https://replimune.com/clinical-trials/ignyte-3/.

About  Replimune  
Replimune Group, Inc., headquartered in  Woburn, MA, was founded in 2015 with the mission to transform cancer treatment by pioneering the development of novel oncolytic immunotherapies. Replimune’s proprietary RPx platform is based on a potent HSV-1 backbone intended to maximize immunogenic cell death and the induction of a systemic anti-tumor immune response. The RPx platform is designed to have a unique dual local and systemic activity consisting of direct selective virus-mediated killing of the tumor resulting in the release of tumor derived antigens and altering of the tumor microenvironment to ignite a strong and durable systemic response. The RPx product candidates are expected to be synergistic with most established and experimental cancer treatment modalities, leading to the versatility to be developed alone or combined with a variety of other treatment options. For more information, please visit  www.replimune.com.

Forward Looking Statements
This press release contains forward looking statements within the meaning of Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended, including statements regarding the design and advancement of our clinical trials, the timing and sufficiency of our clinical trial outcomes to support potential approval of any of our product candidates, our goals to develop and commercialize our product candidates, patient enrollments in our existing and planned clinical trials and the timing thereof, and other statements identified by words such as could, expects, intends, may, plans, potential, should, will, would, or similar expressions and the negatives of those terms. Forward-looking statements are not promises or guarantees of future performance and are subject to a variety of risks and uncertainties, many of which are beyond our control, and which could cause actual results to differ materially from those contemplated in such forward-looking statements. These factors include risks related to our limited operating history, our ability to generate positive clinical trial results for our product candidates, the costs and timing of operating our in-house manufacturing facility, the timing and scope of regulatory approvals, the availability of combination therapies needed to conduct our clinical trials, changes in laws and regulations to which we are subject, competitive pressures, our ability to identify additional product candidates, political and global macro factors including the impact of the coronavirus as a global pandemic and related public health issues and the Russian-Ukrainian and Israel-Hamas political and military conflicts, and other risks as may be detailed from time to time in our Annual Reports on Form 10-K and Quarterly Reports on Form 10-Q and other reports we file with the  Securities and Exchange Commission. Our actual results could differ materially from the results described in or implied by such forward-looking statements. Forward-looking statements speak only as of the date hereof, and, except as required by law, we undertake no obligation to update or revise these forward-looking statements.

Investor Inquiries
Chris Brinzey
ICR Westwicke
339.970.2843
chris.brinzey@westwicke.com

Media Inquiries
Arleen Goldenberg
Replimune
917.548.1582
media@replimune.com

Source: Replimune Group Inc (NASDAQ:)

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Romanians vote in presidential election focused on high living costs, Ukraine war

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By Luiza Ilie

BUCHAREST (Reuters) -Romanians started voting on Sunday in the first round of a presidential election that may give hard-right politician George Simion a chance of winning, with voters focused on high living costs and the country’s support for Ukraine.

Opinion surveys show leftist Prime Minister Marcel Ciolacu, 56, leader of Romania’s largest party, the Social Democrats, will make it into the run-off vote on Dec. 8, with Simion, 38, of the Alliance for Uniting Romanians the likely runner-up.

About 3.7 million Romanians, or 20.7% of registered voters in the European Union and NATO state, had cast their ballots across the country by 1045 GMT, data showed. Voting ends at 1900 GMT with exit polls to follow immediately.

Voting by Romanians abroad, who can influence the result and where the hard right leader is popular, began on Friday.

Analysts expect Ciolacu to win the second round against Simion, appealing to moderates and touting his experience running Romania during a war next door.

But the prospect of a Ciolacu-Simion run-off vote could mobilise centre-right voters in favour of Elena Lasconi, leader of opposition Save Romania Union, ranked third in opinion surveys, analysts said.

Simion has cast the election as a choice between an entrenched political class beholden to foreign interests in Brussels and himself, an outsider who will defend Romania’s economy and sovereignty.

He opposes military aid to Ukraine and supports a peace plan as envisioned by U.S. President-elect Donald Trump, whom he admires, and would support a government that emulates that of Italy’s Giorgia Meloni.

“We want peace, the war must end so we stop being afraid,” 76-year-old Valentin Ion said after voting in Bucharest.

“Politicians must be more understanding and give money to the needy.”

Romania has the EU’s largest share of people at risk of poverty. Ciolacu’s coalition government of his Social Democrats (PSD) and centre-right Liberals has raised the minimum wage and increased pensions twice this year, but high budget spending has swollen deficits and kept inflation high.

“I am taking my parents and my children to go vote for PSD, it is the best party, Marcel Ciolacu gave us so much,” said Vasile Popa, 46.

Since Russia attacked Ukraine in 2022, Romania has enabled the export of millions of tons of grain through its Black Sea port of Constanta and provided military aid, including the donation of a Patriot air defence battery.

FAMILY VALUES

“The outcome is still very difficult to predict due to the high concentration of candidates and the splitting of the centre-right vote,” said Sergiu Miscoiu, a political science professor at Babes-Bolyai University.

Most candidates, he said, have campaigned on conservative messages such as protecting family values.

“Mainstream party candidates have a very catch-all message, on the one hand the nation, the army, religion and so on. On the other hand, we see a commitment to Europe, although it is seen more as a revenue source than an inspiration for values.”

© Reuters. A voter exits a voting booth, on the day of the first round of the presidential election in Bucharest, Romania, November 24, 2024. REUTERS/Andreea Campeanu

Outgoing two-term president Klaus Iohannis, 65, had cemented Romania’s strong pro-Western stance but was accused of not doing enough to fight corruption.

Romania’s president, limited to two five-year terms, has a semi-executive role which includes heading the armed forces.

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Israeli army orders Gaza City suburb evacuated, spurring new wave of displacement

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By Nidal al-Mughrabi

CAIRO (Reuters) -The Israeli military issued new evacuation orders to residents in areas of an eastern Gaza City suburb, setting off a new wave of displacement on Sunday, and a Gaza hospital director was injured in an Israeli drone attack, Palestinian medics said.

The new orders for the Shejaia suburb posted by the Israeli army spokesperson on X on Saturday night were blamed on Palestinian militants firing rockets from that heavily built-up district in the north of the Gaza Strip.

“For your safety, you must evacuate immediately to the south,” the military’s post said. The rocket volley on Saturday was claimed by Hamas’ armed wing, which said it had targeted an Israeli army base over the border.

Footage circulated on social and Palestinian media, which Reuters could not immediately verify, showed residents leaving Shejaia on donkey carts and rickshaws, with others, including children carrying backpacks, walking.

Families living in the targeted areas began fleeing their homes after nightfall on Saturday and into Sunday’s early hours, residents and Palestinian media said – the latest in multiple waves of displacement since the war began 13 months ago.

In central Gaza, health officials said at least 10 Palestinians were killed in Israeli airstrikes on the urban camps of Al-Maghazi and Al-Bureij since Saturday night.

Adding to the miseries of Gaza’s 2.3 million people, most of whom have been repeatedly displaced, heavy winter rain flooded hundreds of tents across the enclave, spoiling food and sweeping away plastic and cloth sheeting that had protected them against the elements.

“We ran in the middle of the night, the rainwater flooded the tent, the food is gone, the kids screamed and I am afraid they will get sick,” Rami, 37, a Gaza City man displaced at a former soccer stadium, told Reuters via a messaging app.

The Palestinian Civil Emergency Service said thousands of displaced people were impacted by the seasonal flooding and demanded new tents and caravans from aid donors to shield them.

HOSPITAL DIRECTOR WOUNDED BY GUNFIRE

In north Gaza, where Israeli forces have been operating against regrouping Hamas militants since early last month, health officials said an Israeli drone dropped bombs on Kamal Adwan Hospital, injuring its director Hussam Abu Safiya.

“This will not stop us from completing our humanitarian mission and we will continue to do this job at any cost,” Abu Safiya said in a video statement circulated by the health ministry on Sunday.

“We are being targeted daily. They targeted me a while ago but this will not deter us…,” he said from his hospital bed.

Israeli forces say armed militants use civilian buildings including housing blocks, hospitals and schools for operational cover. Hamas denies this, accusing Israeli forces of indiscriminately targeting populated areas.

Kamal Adwan is one of three hospitals in north Gaza that are barely operational as the health ministry said the Israeli forces have detained and expelled medical staff and prevented emergency medical, food and fuel supplies from reaching them.

In the past few weeks, Israel said it had facilitated the delivery of medical and fuel supplies and the transfer of patients from north Gaza hospitals in collaboration with international agencies such as the World Health Organization.

Residents in three embattled north Gaza towns – Jabalia, Beit Lahiya and Beit Hanoun – said Israeli forces had blown up hundreds of houses since renewing operations in an area that Israel said months ago had been cleared of militants.

Palestinians say Israel appears determined to depopulate the area permanently to create a buffer zone along the northern edge of Gaza, an accusation Israel denies.

© Reuters. Displaced Palestinian children stand near tents following rainfall, amid the Israel-Hamas conflict, in Gaza City November 24, 2024. REUTERS/Dawoud Abu Alkas

Israel’s campaign in Gaza has killed more than 44,000 people, uprooted nearly the entire population at least once, according to Gaza officials, while reducing wide swathes of the narrow coastal territory to rubble.

The war erupted in response to a cross-border attack by Hamas-led militants on Oct. 7, 2023 in which gunmen killed around 1,200 people and took more than 250 hostages back to Gaza, according to Israeli tallies.

(Reporting and writing by Nidal al-Mughrabi; editing by Mark Heinrich)

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Green activists in S. Korea demand tough action on plastic waste at UN talks

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By Minwoo Park and Daewoung Kim

BUSAN, South Korea (Reuters) – Hundreds of environmental campaigners marched on Saturday in the South Korean city of Busan to demand stronger global commitments to fight plastic waste at U.N. talks in the city next week.

About a thousand people, including members of indigenous groups, young people and informal waste collectors, took part in the rally, the organiser said, with some carrying banners saying “Cut plastic production” and “Drastic plastic reduction now!”.

The activists marched around the Busan Exhibition and Convention Centre, where the fifth session of the Intergovernmental Negotiating Committee (INC-5) will take place from Monday to discuss a legally binding global agreement on plastic pollution.

Debate is expected to focus on whether the deal should seek to slash production, while major producers such as Saudi Arabia and China have said in previous rounds that it should prioritise less contentious strategies, such as waste management.

“We are here with Greenpeace and our allies in the Break Free from Plastic movement to represent the millions of people around the world that are demanding that world leaders address plastic pollution by reducing the amount of plastic that we produce in the first place,” said Graham Forbes, global plastic campaign lead at Greenpeace.

People from different countries and of all ages took part in Saturday’s rally and some wore elaborate, decorated hats made from discarded plastic items.

“It looks like the Earth, and a living creature, because I wanted to say our living creatures are being affected by plastic pollution,” said Lee Kyoung-ah, 52, who was wearing a hat made of abandoned plastic buoy.

Lee Min-sung, 26, said he also hoped to see changes in everyday consumer habits.

© Reuters. Climate activists march on a street to demand stronger global commitments to fight plastic waste at the upcoming fifth session of the Intergovernmental Negotiating Committee (INC-5), in Busan, South Korea, November 23, 2024.   REUTERS/Minwoo Park

“I hope the culture of using ‘reusables’ becomes a cool, trendy movement, as that will reduce (waste) little by little,” said Lee, who brought his lunch from home in a glass container.

“I will pick up trash more often, whenever I have time, and throw away less to save the Earth,” said fourth-grader Kim Seo-yul, who flew from her home in Jeju Island to join the march.

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