On December 2, 2018 NewLink Genetics Corporation (NASDAQ:NLNK) reported that updated Phase 1 data evaluating indoximod plus standard-of-care chemotherapy for the treatment of adult patients with newly diagnosed acute myeloid leukemia (AML) were presented today by Ashkan Emadi, MD, PhD, Professor of Medicine and Associate Director for Clinical Research, University of Maryland Greenebaum Comprehensive Cancer Center, in an oral session today at the 60thAmerican Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting in San Diego, CA, from 9:30AM – 11:00AM PT, in Grand Hall B, Manchester Grand Hyatt (Press release, NewLink Genetics, DEC 2, 2018, View Source [SID1234531779]).

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This Phase 1 trial evaluated the initial safety and preliminary evidence of clinical activity of adding indoximod to standard 7+3 induction and high-dose cytarabine (HiDAC) consolidation chemotherapy for adult patients with newly diagnosed AML. The presentation highlighted an initial safety profile indicating that the treatment regimen was well tolerated with adverse events commensurate with chemotherapy alone. Evidence of clinical activity was observed for indoximod plus chemotherapy in newly diagnosed AML as supported by these Phase 1 data showing post-induction minimal residual disease (MRD) negativity rate of 86% and post-HiDAC1 MRD negativity of 100%.

"These data demonstrate the promising potential for indoximod in combination therapy for patients with newly diagnosed AML and the use of MRD status as a study endpoint," said Dr. Ashkan Emadi. "We remain encouraged and look forward to additional data as this study proceeds."

Fifty-seven patients were screened, and 38 patients initiated induction therapy on protocol. Five patients never received indoximod resulting in an intent-to-treat (ITT) population of 33 patients. Twenty-two patients received the pre-specified 80% of indoximod dosing required to be included in the per protocol (PP) analysis, 8 received less than 80% of the scheduled indoximod dosage, and 3 patients remained on induction treatment as of the date of data cut off. Of these 22 PP patients, 16/22 (73%) achieved complete morphological response (CR) and 6 were primary refractory. Of the patients who achieved CR, 14 had results available from MRD testing post-induction. MRD negativity was defined by a flow cytometry assay at a level of < 0.02% (Hematologics, Inc., Seattle, WA). Of those tested, 12/14 (86%) were MRD-negative. Of the 14 patients, 1 patient proceeded to transplant, and 13 began HiDAC consolidation therapy. Post-HiDAC consolidation, all 13 patients were tested for MRD status with all 13/13 (100%) reported to be MRD-negative. When benchmarked against available published studies, these initial data appear encouraging. For a more precise comparison, a contemporaneous multi-institutional dataset is being aggregated to benchmark these data against data generated from patients undergoing the same chemotherapy regimen without the addition of indoximod using the same MRD assay assessed at the same reference laboratory.

Safety data from this Phase 1 trial indicate that the combination therapy regimen was well tolerated. No RLTs were observed when combining indoximod with standard-of-care chemotherapy. Grade 3 or greater adverse hematologic events included febrile neutropenia, anemia, and thrombocytopenia while non-hematologic events included hypoxia, anemia, and pneumonia. The overall adverse event profile observed in this small sample size is consistent with that of 7+3 induction chemotherapy plus HiDAC consolidation alone.

About AML1,2

Adult acute myeloid leukemia (AML) is a cancer of the blood and bone marrow in which the bone marrow makes abnormal types of white blood cells, red blood cells, or platelets. AML is the most common type of acute leukemia in adults and tends to progress rapidly without treatment. In the US, approximately 19,000 patients per year are diagnosed with AML with only around 25% expected to survive longer than three years. Of those newly diagnosed patients, approximately half are categorized as young and fit for an aggressive chemotherapy treatment regimen.

1National Cancer Institute
2American Society of Clinical Oncology

About Indoximod

Indoximod is an investigational, orally available small molecule targeting the IDO pathway. The IDO pathway is a key immuno-oncology target, suppressing immune response and allowing for immune escape by degrading tryptophan with the resultant production of kynurenine. Indoximod reverses the immunosuppressive effects of low tryptophan and high kynurenine through mechanisms that include modulation of the AhR-driven transcription of genes that control immune function. This results in increased proliferation of effector T cells, increased differentiation into helper T cells rather than regulatory T cells, and downregulation of IDO expression in dendritic cells. Indoximod is being evaluated in combination with treatment regimens including chemotherapy, radiation, checkpoint blockade and cancer vaccines across multiple indications including recurrent pediatric brain tumors, DIPG, and AML.

On December 2, 2018 MorphoSys reported its Updated Data from L-MIND Study of MOR208 in combination with Lenalidomide in r/r DLBCL at ASH (Free ASH Whitepaper) 2018 (Press release, MorphoSys, DEC 2, 2018, View Source [SID1234531777])

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MorphoSys AG (FSE: MOR; Prime Standard Segment; MDAX & TecDAX; Nasdaq: MOR) presented data from the ongoing single-arm phase 2 clinical trial known as L-MIND in an oral presentation at the 60th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting 2018 in San Diego, USA. L-MIND is designed to investigate the antibody MOR208 in combination with lenalidomide in patients with relapsed or refractory diffuse large B cell lymphoma (r/r DLBCL) who are not eligible for high-dose chemotherapy (HDC) and autologous stem cell transplantation (ASCT). MOR208 is an investigational humanized Fc-enhanced monoclonal antibody directed against CD19 and is currently in clinical development in blood cancer indications.

The L-MIND study enrolled patients with r/r DLBCL, who are ineligible for HDC and ASCT, after up to three prior lines of therapy, with at least one prior therapy including an anti-CD20 targeting therapy, such as rituximab. The updated interim data reported today (cut-off date June 5, 2018) included all 81 patients enrolled in the L-MIND trial, with a median observation time of 12 months. Efficacy results in this update are based on assessment by the investigators for all 81 patients. Patients enrolled had a median age of 72 years and had received a median of two prior treatment lines.

The data showed a response in 47 out of 81 patients (overall response rate, or ORR, 58%), with complete responses (CR) in 27 (33%) and partial responses (PR) in 20 (25%) patients. The median progression-free survival (mPFS) was 16.2 months (95% confidence interval (CI) 6.3 months – not reached). Responses were durable with the median duration of response (DoR) not reached (95% CI: NR – NR) and 70% of responding patients were without progression at 12 months (12-month DoR rate: 70%, Kaplan-Meier estimate). A significant proportion of patients (37/81; 46%) were still on study treatment, with 19 having been treated for over 12 months. Median overall survival (OS) was not reached (95% CI: 18.6 months – NR); the 12-month OS rate was 73% (95% CI: 63% – 85%).

Efficacy parameters, such as response rates and median PFS showed comparable results in most patient subgroups of interest, including low/low-intermediate versus intermediate-high/high IPI score, rituximab refractory versus not refractory and primary refractory versus not refractory, amongst others.

No unexpected toxicities were observed for the treatment combination and no infusion-related reactions (IRRs) were reported for MOR208. The most frequent treatment-emergent adverse events (TEAEs) with a toxicity grading of 3 or higher were neutropenia in 35 (43%), thrombocytopenia in 14 (17%), and anemia in 7 (9%) patients each. Treatment-related serious adverse events (SAEs) occurred in 16 (19.8%) patients, the majority of which were infections or neutropenic fever. 41 (50.6%) patients required dose reduction with lenalidomide, 58 patients (72%) could stay on a daily lenalidomide dose of 20 mg or higher.

The results reported today confirm data from earlier interim analyses reported from this trial in March 2018, when 68 patients had been eligible for investigators’ efficacy assessment at the Dec 12, 2017 cut-off date.

"Patients with relapsed or refractory DLBCL who, after having failed initial therapies, are ineligible for high-dose chemotherapy (HDC) and autologous stem cell transplantation (ASCT), need more treatment options," commented Dr. Malte Peters, Chief Development Officer of MorphoSys AG. "We are encouraged by our most recent clinical data from the ongoing L-MIND trial. These support our plan to develop MOR208 in combination with lenalidomide, based on our current FDA breakthrough therapy designation, as a potential chemo-free treatment option for this patient population."

Details about the presentation on L-MIND data at ASH (Free ASH Whitepaper) 2018:

Abstract publication number: 227
Session name: 626. Aggressive Lymphoma (Diffuse Large B-Cell and Other Aggressive B-Cell Non-Hodgkin Lymphomas)-Results from Prospective Clinical Trials"
Session date and time: Saturday, December 1, 2018, 4:00pm-5:30pm PST
Presentation time: 5:00pm PST
Room: Marriot Marquis San Diego Marina, Pacific Ballroom 20, San Diego, California.

MorphoSys will hold an investor & analyst event after the 60th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting 2018 on December 5, 2018, 10:00am EST (3:00pm GMT, 4:00pm CET) in New York. The presentation, a live webcast and a replay of the webcast will be made available at View Source

About DLBCL
Diffuse large B-cell lymphoma (DLBCL) is the most frequent type of malignant lymphoma worldwide and accounts for approximately 30% of all non-Hodgkin lymphomas. Between 30% and 40% of all patients with DLBCL either fail to respond to or show a relapse to initial therapy. Patients who failed frontline therapy and are not eligible to high dose chemotherapy (HDC) and autologous stem cell transplantation (ASCT) are reported to have a poor outcome and require more therapeutic options.

About CD19 and MOR208
CD19 is broadly and homogeneously expressed across different B cell malignancies including DLBCL and CLL. CD19 has been reported to enhance B cell receptor (BCR) signaling, which is assumed important for B cell survival, making CD19 a potential target in B cell malignancies.
MOR208 is an investigational humanized Fc-engineered monoclonal antibody directed against CD19. Fc-modification of MOR208 is intended to lead to a significant potentiation of antibody-dependent cell-mediated cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP), thus aiming to improve a key mechanism of tumor cell killing. MOR208 has been observed in preclinical models to induce direct apoptosis by binding to CD19, which is assumed to be involved in B cell receptor (BCR) signaling.
MorphoSys is clinically investigating MOR208 as a therapeutic option in B cell malignancies in a number of ongoing combination trials. An open-label phase 2 combination trial (L-MIND study) is investigating the safety and efficacy of MOR208 in combination with lenalidomide in patients with relapsed/refractory DLBCL who are not eligible for high-dose chemotherapy (HDC) and autologous stem cell transplantation (ASCT). Based on interim data from L-MIND, in October 2017 the U.S. FDA granted Breakthrough Therapy Designation for MOR208 plus lenalidomide in this patient population. The pivotal phase 2/3 B-MIND study is designed to investigate MOR208 in combination with the chemotherapeutic agent bendamustine in patients with relapsed/refractory DLBCL who are not eligible for high-dose chemotherapy (HDC) and autologous stem cell transplantation (ASCT) in comparison to the combination of the anti-CD20 antibody rituximab plus bendamustine. In addition, MOR208 is currently being investigated in patients with relapsed/refractory CLL/SLL after discontinuation of a prior Bruton tyrosine kinase (BTK) inhibitor therapy (e.g. ibrutinib) in combination with idelalisib or venetoclax.

On December 2, 2018 Novartis reported its results of a retrospective, real-world evidence study in patients with immune thrombocytopenia (ITP) treated with Revolade (eltrombopag), compared to other second-line therapies (Press release, Novartis, DEC 2, 2018, View Source [SID1234531762]). The data demonstrated that patients experienced better clinical outcomes with Revolade, in terms of fewer bleeding episodes. The data were presented during the 60th Annual Meeting of the American Society of Hematology (ASH) (Free ASH Whitepaper) in San Diego.

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"Despite advances in treating immune thrombocytopenia, many patients remain at risk for bleeding episodes," said Samit Hirawat, MD, Head, Novartis Oncology Global Drug Development. "With these kind of real-world data, we can reimagine care by more clearly understanding the outcomes of a range of treatments and, in turn, helping healthcare providers better navigate available options with their patients."

Electronic health records (EHR) data from January 1, 2009 to September 30, 2016 from the Optum EHR database were used to evaluate the effect of second-line agents for ITP. Identified patients had the following characteristics: 18 years or older, evidence of previous treatment with steroids or immune globulin products, and activity in the database for at least 6 months prior to and 12 months post initiation of a second-line agent. Treatment outcomes evaluated included platelet counts, bleeding related episodes (BREs), and thrombotic events (TEs) over the 12-month period following starting a second-line therapy.

Of the 2,526 adults that met the inclusion criteria, 110 (4.4%) received eltrombopag, 189 (7.5%) romiplostim, 1,488 (58.9%) rituximab, and 260 (10.3%) splenectomy, with the remaining 479 (18.9%) receiving a mix of other second-line agents. Compared to baseline, platelet counts increased in all treatment cohorts. The proportion of patients who experienced BREs ranged from 25.5% (eltrombopag) to 36.5% (romiplostim), while TEs were observed in all treatment cohorts ranging from 11.6% (eltrombopag) to 15.7% (splenectomy). An additional analysis demonstrated that patients with ITP who had a splenectomy as second-line treatment had the highest mean platelet counts during the first 12 months post treatment initiation, but were at greatest risk for TEs (15.7%) (e.g., stroke, transient ischemic attack, myocardial infarction, deep vein thrombosis, and pulmonary embolism) compared to 11.6% (eltrombopag), 12.7% (romiplostim), and 13.9% (rituximab).

"These real-world data can help doctors as they weigh options for second-line therapy with their patients." Adam Cuker, MD, Assistant Professor of Medicine at the University of Pennsylvania. "They may also help explain the long-term trend toward deferring splenectomies until after other lines of treatment have been tried."

Immune thrombocytopenia is a rare and potentially serious blood disorder where there is an increased risk of bleeding due to a low number of platelets. As a result, patients with ITP experience bruising, bleeding and, in rare cases, serious hemorrhage that can be fatal.[1] The goal of treatment in chronic/persistent ITP is to maintain a safe platelet count that reduces the risk of bleeding.[1]

Promacta/Revolade (eltrombopag)
Eltrombopag, marketed as Promacta in the US and Revolade in countries outside the US, is approved in more than 90 countries worldwide for the treatment of thrombocytopenia in adult patients with chronic immune thrombocytopenic purpura (ITP) who have had an inadequate response or are intolerant to other treatments. It is also approved for the treatment of patients with severe aplastic anemia (SAA) as first-line therapy in the US (patients 2 years and older) and Japan, and in many other countries for patients who are refractory to other treatments. In more than 40 countries, Promacta/Revolade is indicate for the treatment of thrombocytopenia in patients with chronic hepatitis C to allow them to initiate and maintain interferon-based therapy. Promacta/Revolade is approved in the US and in the European Union for the treatment of thrombocytopenia in pediatric patients 1 year and older with chronic immune thrombocytopenia (ITP) who have had an insufficient response to corticosteroids, immunoglobulins, or splenectomy. Promacta should only be used in patients with ITP whose degree of thrombocytopenia and clinical condition increase the risk for bleeding.

Important Safety Information
Promacta can cause serious side effects, including liver problems, abnormal liver function tests, high platelet counts and higher risk for blood clots, and new or worsened cataracts (a clouding of the lens in the eye).

Promacta is not for treatment of people with a precancerous condition called myelodysplastic syndromes (MDS). If you have MDS and receive Promacta, your MDS condition may worsen and become AML. If MDS worsens to become AML, you may die sooner from AML.

For patients who have chronic hepatitis C virus and take Promacta with interferon and ribavirin treatment, Promacta may increase the risk of liver problems. Patients should tell a healthcare provider right away if they have any of these signs and symptoms of liver problems including yellowing of the skin or the whites of the eyes (jaundice), unusual darkening of the urine, unusual tiredness, right upper stomach area pain, confusion, swelling of the stomach area (abdomen).

A healthcare provider will order blood tests to check the liver before starting Promacta and during Promacta treatment. In some cases, treatment with Promacta may need to be stopped due to changes in liver function tests.

The risk of getting a blood clot is increased if the platelet count is too high during treatment with Promacta. The risk of getting a blood clot may also be increased during treatment with Promacta if platelet counts are normal or low. Some forms of blood clots, such as clots that travel to the lungs or that cause heart attacks or strokes can cause severe problems or death. A healthcare provider will check blood platelet counts, and change the dose of Promacta or stop Promacta, if platelet counts get too high. Patients should tell a healthcare provider right away if they have signs and symptoms of a blood clot in the leg, such as swelling, pain, or tenderness in the leg.

People with chronic liver disease may be at risk for a type of blood clot in the stomach area. Patients should tell a healthcare provider right away if they have stomach area pain that may be a symptom of this type of blood clot.

New or worsened cataracts have happened in people taking Promacta. A healthcare provider will check the patient’s eyes before and during treatment with Promacta. Patients should tell a healthcare provider about any changes in eyesight while taking Promacta.

Patients should tell a healthcare provider about all the medicines they take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. Promacta may affect the way certain medicines work. Certain medicines may keep Promacta from working correctly. Patients should take Promacta at least 4 hours before or 4 hours after taking products such as antacids used to treat stomach ulcers or heartburn and multivitamins or products that contain iron, calcium, aluminum, magnesium, selenium, and zinc, which may be found in mineral supplements. Patients should ask a healthcare provider if they are not sure if the medicine is one that is listed above.

Patients should avoid situations and medications that may increase the risk of bleeding while taking Promacta.

The most common side effects of Promacta when used to treat chronic ITP in adults are: nausea; diarrhea; upper respiratory tract infection (symptoms may include runny nose, stuffy nose, and sneezing); vomiting; muscle aches; urinary tract infection (symptoms may include frequent or urgent need to urinate, low fever in some people, pain or burning with urination); pain or swelling (inflammation) in the throat or mouth (oropharyngeal pain and pharyngitis); abnormal liver function tests; back pain; flu-like symptoms (influenza), including fever, headache, tiredness, cough, sore throat, and body aches; skin tingling, itching, or burning; and rash.

The most common side effects of Promacta in children 1 year and older when used to treat chronic ITP are: upper respiratory tract infections (symptoms may include runny nose, stuffy nose, and sneezing); pain or swelling (inflammation) in the nose and throat (nasopharyngitis); cough; diarrhea; pyrexia; runny, stuffy nose (rhinitis); stomach (abdominal) pain; pain or swelling (inflammation) in the throat or mouth; toothache; abnormal liver function tests; rash; runny nose (rhinorrhea).

The most common side effects when Promacta is used in combination with other medicines to treat chronic HCV are: low red blood cell count (anemia); fever; tiredness; headache; nausea; diarrhea; decreased appetite; flu-like symptoms (influenza), including fever, headache, tiredness, cough, sore throat, and body aches; feeling weak; trouble sleeping; cough; itching; chills; muscle aches; hair loss; and swelling in the ankles, feet, and legs.

The most common side effects of Promacta when used to treat severe aplastic anemia (SAA) are: nausea, feeling tired, cough, diarrhea, headache, pain in arms, legs, hands or feet, shortness of breath, fever, dizziness, pain in nose or throat, abdominal pain, bruising, muscle spasms, abnormal liver function tests, joint pain, and runny nose. Laboratory tests may show abnormal changes to the cells in bone marrow.

The most common side effects of Promacta when used to treat adults and pediatric patients 2 years and older with SAA in combination with standard immunosuppressive therapy are: abnormal liver function tests, rash and skin discoloration including darkening of skin patches
(hyperpigmentation).

On December 1, 2018 Oncopeptides AB (Nasdaq Stockholm: ONCO) reported a presentation of the first interim data with melflufen (Ygalo) from the ongoing phase I/II study ANCHOR at the 60th ASH (Free ASH Whitepaper) meeting in San Diego, California, USA (Press release, Oncopeptides, DEC 1, 2018, View Source [SID1234531802]).

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Overall conclusions

The combinations of melflufen and dexamethasone (dex) with either bortezomib or daratumumab in relapsed-refractory multiple myeloma (RRMM) patients are well tolerated
No dose limiting toxicity has been observed at the melflufen 30 and 40 mg dose levels in either regimens. The 40 mg dose level is still recruiting patients
An Overall Response Rate (ORR) of 86% was observed with melflufen and dexamethasone in combination with daratumumab (CD38-directed monoclonal antibody)
An Overall Response Rate (ORR) of 100% was observed with melflufen and dexamethasone in combination with bortezomib (proteasome inhibitor)
The data are presented in a poster that can be found at: www.oncopeptides.com / presentations / 60th ASH (Free ASH Whitepaper)

CEO comments

"Although, these are early data and small patient samples, it is encouraging to see that melflufen is well tolerated and has a very high level of activity with no cross resistant pattern in combination regimens. These patients have undergone 2-3 prior lines of therapy and have developed resistant disease. The interim data show a very good efficacy profile for melflufen in combination with either bortezomib or daratumumab. In a cross-study comparison in RRMM patients treated with combination regimens our interim data with an ORR in the range 86-100% stand out positively. The treatment landscape changes over time and there is a high need of new treatment options with a novel mechanism of action like melflufen" said Jakob Lindberg, CEO of Oncopeptides.

About the ANCHOR study

The study recruitment is ongoing. ANCHOR is a phase I/II study where melflufen and dexamethasone (dex) is dosed in combination with either bortezomib or daratumumab. All patients must have 1-4 prior lines of therapy and be refractory (or intolerant) to an immunomodulary agent (IMiD) or a proteasome inhibitor (PI) or both.

In combination with bortezomib (Regimen A) patients cannot be refractory to a PI and in combination with daratumumab (Regimen B) patients cannot be previously exposed to any anti-CD38. Patients will be treated until documented disease progression or unacceptable toxicity. The primary objective of the phase I part of the study is to determine the optimal dose of melflufen and dex, up to a maximum of 40 mg, in combination with bortezomib or daratumumab. An additional 20 patients per regimen will be recruited in the phase II part of the study where the primary objective is ORR.

Summary of the ANCHOR interim data

Melflufen in combination with bortezomib – Regimen A

At the time of the data cut-off November 12, 2018, 3 patients had been treated with 30 mg melflufen and dex in combination with bortezomib. Median age was 81 years with a median of 3 prior lines of therapy. All patients were relapsed-refractory and 2 out of 3 patients were last line refractory (disease progression while on therapy). All patients were ongoing at the time of the data cut-off with a median treatment duration of 5.8 months.

The patients received a total of 17 cycles of treatment with a median of 7. All 3 patients achieved partial response (PR). No dose limiting toxicities were observed at the 30 mg melflufen dose level and the melflufen 40 mg has been opened for enrollment. The regimen was well tolerated with clinically manageable G3/4 hematological AEs and the low number of non-hematological AEs was noteworthy.

Melflufen in combination with daratumumab – Regimen B

At the time of the data cut-off, November 12, 2018, 9 patients had been treated with melflufen in combination with daratumumab and dex. Median age was 63 years with a median of 2 prior lines of therapy. No patient had achieved CR in any previous line of therapy, 67% were IMiD refractory and 56% were last line refractory (disease progression while on therapy). All patients were ongoing at the time of the data cut-off.

All 9 patients were still ongoing with a median treatment duration of 3.9 months. They received a total of 39 cycles of treatment with a median of 4.

Overall response rate N/A*
ORR CR VGPR PR MR SD PD
total, N=9 86% 0 4 2 0 1 0 2
*2 of the 9 patients were still in their first cycle of treatment and were therefore not evaluable for response as described at time for data cut.

4 patients were treated with 30 mg melflufen and 5 patients were treated with 40 mg melflufen with no dose limiting toxicity observed. The combination of melflufen, dexamethasone and daratumumab was well tolerated with clinically manageable G3/4 hematological AEs and the low number of non-hematological AEs was noteworthy.

About Melflufen

Melflufen (Ygalo), a peptide conjugated alkylator belonging to a novel class of peptidase-enhanced compounds, targets multiple myeloma (MM) cells with a unique mechanism of action. Aminopeptidases are enzymes found in all cells but are over-expressed in several cancers including MM. Ygalo selectively targets MM cells through aminopeptidase-driven accumulation. In vitro experiments show a 50-fold enrichment of the active substance in MM cells compared with administration of equal amount of an alkylator not enriched by aminopeptidases. The enrichment results in selective cytotoxicity (increased on-target potency and decreased off-target toxicity), and that resistance pathways of existing myeloma treatments (including alkylators) is overcome. Melflufen also demonstrates strong anti-angiogenic properties.

Melflufen in clinical development

Melflufen (Ygalo) has been used to treat late-stage RRMM patients in both phase I and phase II clinical studies (O-12-M1) with favorable results. Currently, melflufen is being studied in four clinical trials for the treatment of multiple myeloma. The current studies are OCEAN, HORIZON, ANCHOR and BRIDGE.

The current clinical study program is intended to demonstrate better results from treatment with melflufen compared to established alternative drugs for patients with multiple myeloma. Melflufen could potentially provide physicians with a new treatment option for patients suffering from this serious disease.

Melflufen has been investigated in the treatment of late-stage relapsed refractory multiple myeloma (RRMM) patients. This was done in the clinical study O-12-M1 where strong final results were reported in December 2017. Currently, four clinical studies are ongoing with melflufen.

OCEAN is Oncopeptides pivotal Phase III study where melflufen is compared directly with current standard of care, pomalidomide, in late-stage RRMM patients.

HORIZON is a Phase II study that studies the effect of melflufen in late-stage RRMM patients with few or no remaining established treatment options. Updated interim data from this study will be presented at ASH (Free ASH Whitepaper) in December 2018.

ANCHOR is a phase I/II study where melflufen is administered in combination with either bortezomib or daratumumab in RRMM patients. The results of this study aim to create understanding and knowledge among treating physicians for how melflufen can be used in combination with these drugs. In addition, the results could open up for the use of melflufen in earlier lines of treatment.

BRIDGE is a phase II study, where melflufen is used in RRMM patients with impaired renal function. This is a positioning study to show melflufen’s treatment profile in these patients.

On December 1, 2018 MaaT Pharma reported the results from its ODYSSEE (NCT02928523) Phase 1b/2a clinical trial demonstrating that the Company’s proprietary MaaT Microbiome Restoration Biotherapeutic (MMRB) therapeutic is able to restore a functional microbiome in acute myeloid leukemia (AML) patients after having undergone intensive chemotherapy and multiple courses of antibiotics (Press release, MaaT Pharma, DEC 1, 2018, View Source [SID1234531791]). The study was designed to investigate the safety and feasibility of reestablishing a functional microbiome using MaaT Pharma’s therapeutic as well as evaluating initial signs of efficacy including reduction of intestinal inflammation and the control of detrimental antibiotic-resistant bacteria. Due to the harsh treatment regimens, AML patients lose their functional microbiome and experience a variety of severe complications that dramatically impact outcomes and quality of life. MaaT Pharma’s MMRB therapeutic aims to restore microbiome function and improve clinical outcomes in these patients. The data were presented at 6:15 pm Pacific Time on December 1st, 2018 at the 60th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition held in San Diego, California.

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In total 25 AML patients were treated in the clinical trial. At the time of admission, fecal microbiota was collected from each patient, conditioned, processed and frozen according to GMP conditions. Following the first round of chemotherapy and antibiotic treatment, patients were administered two doses of the collected fecal microbiota as an enema 24 hours apart after hematopoietic recovery and before undergoing the second round of chemotherapy. Blood and fecal samples were collected on three separate days, (1) on day 0, at the time of patient inclusion in the trial, (2) on day 29, following hematopoietic recovery after the first round of intensive treatments and (3) on day 40, before the start of the consolidation chemotherapy. Microbiome profile evolution was analyzed using high-resolution metagenome sequencing and patient follow-up was scheduled for 6 months and 12 months after inclusion.

"The results from the ODYSSEE clinical trial are impressive and demonstrate proof-of-concept for the ability of our approach to restore a functional microbiome, following antibiotics and chemotherapies, in AML patients and that reestablishing the microbiome has the potential to improve survival outcomes," commented Professor Mohamad Mohty, MD, PhD, Professor of Hematology at Sorbonne University and Head of the Hematology and Cellular Therapy Department at the Saint Antoine Hospital in Paris. "Acute myeloid leukemia patients have limited treatment options and the intensive chemotherapy and antibiotic therapy regimens they have to endure significantly contribute to poor quality of life and low survival outcomes. Given these positive results, we look forward to our planned randomized trial with the off-the-shelf capsule formulation MaaT033, as the next step."

Overall, reintroduction of the patient’s own gut microbiome through MaaT Pharma’s proprietary process was well tolerated and no severe adverse events were reported. Metagenomic analysis of the patient samples collected on days 0, 29 and 40 using MaaT Pharma’s proprietary big data analysis platform, GutPrint showed that the MMRB therapeutic restored significantly greater than 90% of the microbial species diversity and structure at day 40, ten days after treatment, including a 43% reduction of the overall expression of antibiotic resistance genes. Most importantly, gut inflammation was significantly reduced to near-baseline levels following MMRB treatment as measured by fecal neopterin biomarker. These results also correlated with the significant reduction of pro-inflammatory bacterial families and restoration of beneficial species among the Lachnospiraceae and Ruminococcaceae families.

"Our commitment has always been to improve outcomes in patients with life-threatening diseases. The results and experience from this trial support our investment in developing standardized, reproducible and high diversity microbiome biotherapeutic products using our MMRB therapeutic and cGMP production facility to treat patients with blood cancers and the complications arising from its treatment," added Hervé Affagard, Co-founder and CEO of MaaT Pharma. "Our lead product, MaaT013, which is manufactured from pooled donors, was developed based on the positive data we collected from this trial and the scientific and clinical evidence showing that restoring the microbiome has therapeutic potential. MaaT013 is currently being tested in a Phase 2 clinical study to treat acute graft-versus-host-disease, a severe consequence of stem cell transplantation. We are also very pleased to have just been awarded Orphan Drug Designation by the EMA for this product after already receiving the designation by the FDA earlier this year."

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