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 * INCINTAS THERAPEUTICS, INC.
   
   ADDRESSING THE MAIN HURDLE IN ACHIEVING PREGNANCY IN ASSISTED REPRODUCTION BY
   REDEFINING THE WAY WE PREPARE THE UTERUS IN ASSISTED REPRODUCTIVE
   TECHNOLOGIES (ART)

 *  * WHAT IS KNOWN:
   
   IT IS IMPERATIVE FOR THE "WINDOW OF IMPLANTATION" TO BE OPEN IN ORDER FOR
   PREGNANCY TO BE ACHIEVED BOTH IN HEALTHY PREGNANCY AND IN ART, (INCLUDING
   IVF, IUI, AI AND TIMED INTERCOURSE TREATMENT). WHEN THIS WINDOW IS CLOSED,
   PREGNANCY IS IMPOSSIBLE BECAUSE THE EMBRYO CANNOT IMPLANT INTO THE UTERINE
   LINING.
   
    
   
   DID YOU KNOW?
   
   ....THAT THE CURRENT IMPLANTATION WINDOW IN ART
   
   IS ONLY "OPEN" FOR 24 HOURS ON AVERAGE, COMPARED TO 4-5 DAYS IN HEALTHY
   PREGNANCY? THIS FACT IS VALIDATED GENOMICALLY AND MORE IMPORTANTLY, THE
   RATE-LIMITING FACTOR IN ACHIEVING
   
   LIVE BIRTH RATE IN ASSISTED REPRODUCTION.
   
    
   
   DOES THIS FACT TROUBLE ANYONE WHO UNDERSTANDS EMBRYOLOGY
   
   AND IS PASSIONATE ABOUT ART,
   
   OTHER THAN INCINTAS THERAPEUTICS?
   
   (IF NOT, IT SHOULD.)
   
    
   
    
   
    
   
    
   
    
   
    
   
   WHEN EXOGENOUS PROGESTERONE IS ADMINISTERED AND REACHES AN IDEAL
   CONCENTRATION RANGE WITHIN UTERINE TISSUE, PREGNANCY OCCURS MORE THAN 80% OF
   THE TIME. THESE FINDINGS ARE CLINICALLY VALIDATED USING GENOMICS ANALYSIS OF
   THE ENDOMETRIUM
   
   THE PROBLEM WITH CONVENTIONAL P ADMINISTRATIONS IS THAT THIS IDEAL
   CONCENTRATION RANGE IS QUICKLY EXCEEDED BECAUSE PLASMA VALUES INCREASE
   RAPIDLY. THE SYSTEMICALLY-ADMINISTERED PROGESTERONE CANNOT MODULATE AND
   MAINTAIN THE IDEAL P CONCENTRATION (LIKE THE CORPUS LUTEUM DOES IN HEALTHY
   PREGNANCY), DUE TO THE MANNER IN WHICH IT IS ADMINISTERED, THROUGHOUT THE
   WOMAN'S BLOODSTREAM (PERIVAGINALLY AND/OR INTRAMUSCULARLY).
   
    
   
   INCINTAS ADMINISTERS PROGESTERONE WHERE IT IS NEEDED - INSIDE THE UTERUS (NOT
   THE BLOODSTREAM),
   
   WHICH DRAMATICALLY IMPROVES HORMONAL BIOAVAILABILITY AND EXTENDS THE WINDOW
   OF IMPLANTATION 3-4 TIMES LONGER THAN ALL CONVENTIONAL METHODS. INCINTAS USES
   TIME-RELEASED NANOFORMULATION CAPABILITIES THAT PROVIDE THE PRECISE AMOUNT OF
   PROGESTERONE WITHIN THE UTERINE LINING.
   
    
   
   FOR THE FIRST TIME IN NEARLY A HALF CENTURY, INCINTAS TAKES DIRECT CONTROL OF
   RECEPTIVITY WITHIN THE UTERUS.
   
    
   
   INCINTAS THERAPEUTICS HAS PATENTED THIS NOVEL ROUTE OF ADMINISTRATION IN
   ASSISTED REPRODUCTION
   
   TO CORNER THE MARKET OF THIS ADVANCED MEANS OF UTERINE PREPARATION AND
   IMPROVED FERTILITY OUTCOME.
   
    
   
    
   
   ABOUT US
   
   WHAT WE DO
   
   "We intend to move the needle pretty far in assisted reproduction by focusing
   upon failed implantation."
   
   Incintas Therapeutics is comprised of an accomplished team of scientists,
   physicians, geneticists and business professionals who are focused upon
   improving pregnancy outcome in reproductive medicine.
   
   Our sole purpose is to resolve the problem of failed embryonic implantation
   (the main hurdle in achieving pregnancy in IVF) to ultimately encourage
   Single Embryo Transfer (SET) which is more likely to result in a healthy
   singleton pregnancy for the infertile couple.
   
    
   
    

 * EXECUTIVE PARTNERS
   
   ON A MISSION TO HELP MILLIONS OF FERTILITY CHALLENGED FAMILIES
   
   JESSE PIZOLATO
   
   CEO
   
   Founding Partner
   
   MICHAEL BARTON
   
   CFO
   
   Founding Partner
   
   KUN ZOO KIM, MD
   
   FOUNDING PARTNER
   
   

 * SCIENTIFIC PARTNERS
   
   THE EXPERTS BEHIND INCINTAS THERAPEUTICS' BREAKTHROUGH TECHNOLOGY
   
   CARLO BULLETTI, MD, CSO
   
   IVF LUMINARY
   
   Dr Carlo Bulletti is Associate Professor Adjunct at Yale University, New
   Haven (Ct) USA and Director of an IVF program at Extra Omnes Medical Center
   in Cattolica (Italy). He has authored 10 medical text books 130 medical book
   chapters and more than 200 scientific articles.
   
   (www.carlobulletti.com)
   
   ROBERT TAYLOR,
   
   MD, PHD, CMO
   
   ENDOMETRIOSIS LUMINARY
   
   Robert N. Taylor is
   Professor in the Department of Obstetrics and Gynecology and Assistant Dean
   and Director of the MD-PhD Program at University of Buffalo.
   
    
   
    
   
   SANTIAGO MUNNÉ, PHD
   
   HOMU
   
   HEALTH VENTURES
   
   PhD in Human Biology from the University of Pittsburgh and a degree in
   Biology from the Autonomous University of Barcelona. COO at Overture Life.
   Founder of: Reprogenetics, Recombine, Phosphorus, MedAnswers, Overture Life,
   G1 Sciences. Advisory Board (currently): Overture Life, Phosphorus,
   MedAnswers, PreVivo, G1 Sciences.
   
   JOSÉ HORCAJADAS, PHD
   
   HOMU
   
   HEALTH VENTURES
   
   PhD in Molecular Biology and Biochemistry from the Autonomous University of
   Madrid. He has solid experience in the field of Human Reproduction Genetics,
   especially in the area of endometrial receptivity, genomics, transcriptomics,
   implantation and embryo viability.
   
   DAVID COTÁN, PHD
   
   HOMU
   
   HEALTH VENTURES
   
   Doctor in Biotechnology and Degree in Environmental Sciences from the
   University Pablo de Olavide (Seville). Entrepreneur, specialized in technical
   direction and project management in the field of rare diseases, reproduction
   and enzyme scaling in the Andalusian Centre for Developmental Biology.
   
   DELFÍ TORNS
   
   HOMU
   
   HEALTH VENTURES
   
   CEO Programme by IESE, MBA by la Salle University, Bachelor of Arts Degree by
   UOC, Business studies degree and Tourism business studies by the University
   of Barcelona. More than 25 years of executive experience, half of them as
   Managing Director. Active business angel, writer, business consultant, and
   independent advisor.

 * GRAPHICAL ANALYSIS
   
   
   HUMAN IM AND PV ENDOMETRIAL BIOPSY DATA VS. THE INCINTAS INTRAUTERINE
   PROGESTERONE ADVANTAGE
   
   PROGESTERONE CONCENTRATION VS. TIME
   
    
   
    
   
   Finally, an Explanation:
   
   Why Fertility Outcome is Extremely Poor in Assisted Reproduction
   
    
   
   IVF, IUI and Artificial Insemination procedures require hormonal preparation
   to establish receptivity
   
   within the uterus so that a transferred embryo can implant and achieve
   pregnancy. These methods currently use intramuscular injection (IM) and
   perivaginal suppositories (PV) of progesterone whereby the hormone molecules
   travel throughout the bloodstream for 5 days and eventually reach the uterine
   lining (endometrium) where hopeful implantation of the embryo takes place.
   
    
   
   These IM and PV methods are "systemic administrations" because they utilize
   the bloodstream as a means of molecular transport of progesterone to the
   uterus. While systemic administrations of progesterone do achieve pregnancy,
   they simply do not provide the proper bioavailability within the endometrium
   for most of the transferred embryos to implant. In fact, the majority of
   transferred embryos in IVF are introduced to a uterus that is past its
   
   receptive state and in a contraceptive phase, whereby pregnancy is
   impossible.
   
    
   
   In humans, Incintas' scientists demonstrated how progesterone concentration
   within the endometrium
   
   quickly rises to a contraceptive level soon after the uterus establishes
   receptivity
   
   (within 24 hours, average), making pregnancy impossible after that point. The
   scientists demonstrated this discovery using endometrial genomics, a very
   reliable scientific method (ER-Map Study; Enciso, et.al., 2016 and 2018). For
   the first time in history, Incintas' scientific team identified the threshold
   concentration whereby progesterone becomes a contraceptive and further
   demonstrated that once this contraceptive phase is established within the
   endometrial tissue, it is impossible to re-establish receptivity for the
   duration of that IVF treatment. At this point, most of the genomic biomarkers
   have shut down and remain closed until the next ovulatory cycle.
   
    
   
   We all know that embryonic implantation is an extremely complex phenomenon
   and takes a
   
   significant amount of time in the establishment of pregnancy. With an average
   Implantation Window of only 24 hours in all IVF treatments, it should be no
   wonder why pregnancy rates have plateaued to a ~33% rate since the first
   successful IVF birth over four decades ago. With 2.5 million IVF cycles
   performed globally each year this means that about 1.5 million embryos are
   doomed for failure no matter their quality.
   
   .
   
   Similarly, in ruminants (dairy, cattle breeding, etc.)
   systemically-administered progesterone involves the use of PRIDs and CIDR
   suppositories to prime the uterine lining for hopeful implantation of an
   embryo. These products also rely upon the cow's bloodstream and circulatory
   system to transport progesterone molecules to the uterine surface and
   establish receptivity. Similarly to humans, proper bioavailability within the
   cow's endometrium is not achieved for very long, establishing a very short
   estrus time period. This makes estrus determination very difficult for
   farmers who need to determine when their animals are in heat for successful
   reproduction. As a result, heat detection technologies have developed in an
   effort to identify precise timing for IUI, IVF and AI but still, these
   products are difficult to use and largely unsuccessful simply because the
   estrus time period established with these systemic administrations is so
   extremely short.
   
    
   
   It is crucial to understand this point: 
   
   The "Window of Implantation" in humans and "Estrus" in livestock are the ONLY
   periods of time when pregnancy can occur. A perfectly-formed embryo can enter
   the uterus any other time but cannot implant into the uterine lining and
   establish pregnancy because endometrial gene expression is not upregulated.
   This is true in both natural pregnancy and assisted means such as IVF.
   
   These dramatically short time periods of receptivity in humans and livestock
   achieved by systemic progesterone administrations create the bottleneck in
   assisted reproduction.
   
    
   
   And finally, a Solution to the Problem of Failed Implantation
   
    
   
   Incintas Therapeutics eliminates the bottleneck with a novel targeted (and
   patented), intrauterine (IU) route of administration of progesterone. We also
   patented nano/time-release pharmaceutical capabilities to upregulate and
   sustain implantation biomarkers within the endometrium that are associated
   with
   
   the crucial "Window of Implantation" and "Estrus".
   
   Incintas Therapeutics' IU technology enables direct modulation of the genes
   as well as the histologic and biochemical processes associated with
   successful implantation. When an embryo is transferred, embryo-uterine dialog
   time is augmented so that establishment of pregnancy can occur at a
   significantly higher rate
   
   than all other conventional means of uterine hormonal preparation.
   
   And, from the ER-Map Study findings: when the "receptive phase" of the
   endometrium is established,
   
   implantation and pregnancy occurs at an 81.5% Rate.
   
   (This is the potential of Incintas' groundbreaking technology.)
   
    
   
   Finally, after four long decades, there is a genomically-validated means of
   improving fertility outcome
   
   in assisted reproduction.
   
    
   
   Please contact us if you want to know more about Incintas' technology
   
   or wish to become part of this novel paradigm in assisted reproduction.
   
    
   
   Thank you, the Incintas Therapeutics Team

 * A RESULT OF MULTIPLE BIRTH PREGNANCY IN IVF
   
   IN MEMORY OF
   
    
   
    
   
   Mitchell V. Pizolato,
   
   Nov. 23 -Nov. 29, 2000.
   
   Multiple IVF Birth
   
    
   
    
   
    
   
    
   
    
   
    
   
    
   
    
   
    
   
    
   
    
   
    
   
    
   
    
   
   Lance D. Pizolato
   
   Nov. 23 - Dec. 1, 2000
   
   Multiple IVF Birth
   
   Rest in Peace, my dear sons.

 * CONTACT INFORMATION
   
   
   
    
   
   Partnering, Licensing or Collaboration
   
   info@incintas.com
   
   Business Development
   
   jpizolato@incintas.com
   
   mbarton@incintas.com
   
   











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